Sublingual dendritic cells targeting by aptamer: Possible approach for improvement of sublingual immunotherapy efficacy

The efficacy improvement of current sublingual immunotherapy (SLIT) for preventing and treating respiratory airway allergic diseases is the main purpose of many investigations. In this study, we aimed to assess whether ovalbumin (Ova) encapsulated poly (lactic-co-glycolic) acid nanoparticles (PLGA NPs) decorated with dendritic cells (DCs)-specific aptamer could be applied for this purpose.The nanoparticles containing Ova were synthesized by emulsion/solvent evaporation method and attached to DCs-specific aptamer. Ova-sensitized BALB/c mice have been treated in five ways: subcutaneously with free Ova (SCIT), sublingually either with free Ova, Ova-PLGA NPs (two doses), Apt-Ova-PLGA NPs (two doses) and placebo/control Apt-Ova-PLGA NPs. For assessment of immunologic responses, IL-4, IFN-γ, IL-17, IL10, and TGF-β and IgE antibody levels were measured by ELISA and T cell proliferation were evaluated by MTT. In addition, lung and nasal histological examinations, NALF cells counting were carried out. Results declared that the lowest IgE and IL- 4 levels were observed in Apt-Ova-PLGA NPs (both doses). In the other hands, Apt-Ova-PLGA NPs (high dose) showed the highest increase of IFN- γ and TGF- β, decrease of IL-17 levels, total cell count and T-cell proliferation. IL-10 levels showed more decrease in SCIT, Apt-Ova-PLGA NPs (high dose) and Ova-PLGA NPs (high dose) than other groups. Histopathological examinations also confirmed in vitro results. Our findings suggest SLIT with this functionalized delivery system could be a promising approach for promoting the SLIT efficiency by decreasing the required allergen doses through specific delivery of allergen to sublingual DCs and enhancing the suppression of allergic responses.     

Interleukin-2 maintains the survival of interleukin-17+ gamma/delta T cells in inflammation and autoimmune diseases

There is increasing appreciation of the critical pathogenic role of IL-17 in inflammation and autoimmune diseases, which could be produced from both adaptive Th17 cells and innate γδ T cells. Existing evidences suggest that IL-2 is important for in vivo accumulation of IL-17⁺ γδ T cells, leaving the mechanisms still elusive. Herein, using lupus-prone MRL/lpr mice, we demonstrated that splenic γδ T cells were potent IL-17 producers at the onset of lupus, which could be diminished by in vivo IL-2 neutralization. Additional in vivo results showed that neutralization of IL-2 also significantly deleted the IL-17-producing γδ T cells in ovalbumin (OVA) /CFA-immunized B6 mice. Using splenic γδ T cells from OVA/CFA-immunized B6 mice, we further demonstrated that IL-2 could induce IL-17 production alone or together with IL-1β or IL-23 or anti-TCRγδ. Mechanism studies demonstrated that IL-2 could support the survival of γδ T cells, rather than induce the proliferation. Through specific pharmacologic inhibitor, we demonstrated that IL-2 could maintain that RORγt expression of γδ T cells in a STAT5-dependent manner. Collectively, this study suggested that the interplay between IL and 2 and other pro-inflammatory cytokines could trigger the rapid IL-17 production from innate γδ T cells, thus to orchestrate an inflammatory response before the development of adaptive Th17 cells.     

LncRNA AK085865 depletion ameliorates asthmatic airway inflammation by modulating macrophage polarization

Accumulating evidence indicates that regulators of macrophages polarization may play a key role in the development of allergic asthma (AA). However, the exact role of long non-coding RNAs (lncRNAs) in regulating in macrophages polarization in the pathogenesis of dermatophagoides farinae protein 1(Der f1)-induced AA is not fully understood. The purpose of this study was to determine the function of lncRNA AK085865 in regulating macrophages in AA. Here we report that lncRNA AK085865 served as a critical regulator of macrophages polarization and reduced the pathological progress of asthmatic airway inflammation. In response to the challenge of Der f1, AK085865^−/− mice displayed attenuated allergic airway inflammation, including decreased eosinophil in BALF and reduced production of IgE, which were associated with decreased mucous glands and goblet cell hyperplasia. In addition, Der f1-treated AK085865^−/− mice show fewer M2 macrophages when compared with WT asthmatic mice. After adopting bone marrow-derived macrophages (BMDM, M0) from WT mice, Der f1-treated AK085865^−/− mice also revealed a light inflammatory reactions. We further observed that the percentage of type II innate immune lymphoid cells (ILC2s) decreased in AK085865^−/− asthmatic mice. Moreover, M2 macrophages helped promote the differentiation of ILC2s, probably through the exosomal pathway secreted by M2 macrophages. Taken together, these findings reveal that AK085865 depletion can ameliorate asthmatic airway inflammation by modulating macrophage polarization and M2 macrophages can promote the differentiation of innate lymphoid cells progenitor (ILCP) into ILC2s.     

IL-37 is protective in allergic contact dermatitis through mast cell inhibition

Allergic contact dermatitis (ACD), characterized predominantly by erythema, vesiculation, and pruritus, is a T cell-mediated skin inflammatory condition. Among immune cells involved in ACD, mast cells (MCs) play an essential role in its pathogenesis. As an inhibitor of proinflammatory IL-1 family members, interleukin 37 (IL-37) has been shown to ameliorate inflammatory responses in various allergic diseases. In this study, we assessed the immunomodulatory effect of IL-37 on allergic inflammation using a 2,4-dinitrofluorobenzene (DNFB)-induced ACD rat model and isolated rat peritoneal mast cells (RPMCs). Systematic application of IL-37 significantly relieved ear swelling, reduced inflammatory cell infiltration, decreased inflammatory cytokine production (TNF-α, IL-1β, IFN-γ, and IL-13), inhibited MC recruitment, lowered IgE levels, and reduced IL-33 production in the local ear tissues with DNFB challenge. Additionally, RPMCs isolated from ACD rats with IL-37 intervention showed downregulation of IL-6, TNF-α, IL-13, and MCP-1 production following IL-33 stimulation, and reduction of β-hexosaminidase and histamine release under DNP-IgE/HSA treatment. Moreover, IL-37 treatment also significantly restrained NF-κB activation and P38 phosphorylation in ACD RPMCs. SIS3, a specific Smad3 inhibitor, abolished the suppressive effects of IL-37 on MC-mediated allergic inflammation, suggesting the participation of Smad3 in the anti-ACD effect of IL-37. These findings indicated that IL-37 protects against IL-33-regulated MC inflammatory responses via inhibition of NF-κB and P38 MAPK activation accompanying the regulation of Smad3 in rats with ACD.     

Effects of sildenafil on inflammatory injury of the lung in sodium taurocholate-induced severe acute pancreatitis rats

BackgroundInflammatory response and acute lung injury (ALI) occur in sodium taurocholate-induced severe acute pancreatitis (SAP). Because sildenafil has anti-inflammatory, anti-oxidant and immune-modulating effects, we investigated its effect on inflammatory and lung injury in sodium taurocholate-induced SAP-associated ALI rat lung.MethodsSodium taurocholate-induced SAP rats received sildenafil (100 mg/kg) or not and were compared to age-matched normal control animals. We evaluated inflammatory response by detecting the expression of inflammatory factors including IL-1β, IL-6 and TNF-α, and detected the level of lung injury through histopathological evaluation. Moreover, we also tested the protein expression of PCNA, P21, Bcl-2 and Bax in the lung.ResultsSildenafil administration rats had a low level of lung injury and inflammation. In addition, sildenafil significantly increased the expression of proliferation-related markers and decreased the expression of apoptosis-related markers in lung tissue.ConclusionsSildenafil administration may attenuate inflammation and lung injury by promoting proliferation and suppressing apoptosis in SAP rats.     

Tofacitinib suppresses mast cell degranulation and attenuates experimental allergic conjunctivitis

BackgroundAllergic conjunctivitis (AC), a common eye inflammation that affects patients’ health and quality of life, is still a therapeutic challenge for ophthalmologists. Tofacitinib, a new Janus kinase (JAK) inhibitor, has been successfully used in the treatment of several disorders. Nonetheless, its effect in AC and the potential anti-allergic mechanisms are still unclear. The objective of the current study was to explore the roles of tofacitinib in preventing AC and elucidate the potential underlying mechanisms.MethodsTofacitinib was used topically in BALB/c mice with experimental allergic conjunctivitis (EAC). Ocular allergic symptoms and biological modifications were examined. To assess the anti-allergic mechanisms of tofacitinib, RBL-2H3 cells and HUVECs were cultured in vitro. The inhibitory effects and mechanisms of tofacitinib were studied and measured by real-time quantitative PCR, ELISA, western blot analysis, and flow cytometry.ResultsTopical administration of tofacitinib reduced the clinical symptoms of OVA-induced EAC, with a substantial mitigation in inflammatory cell infiltration, histamine release, and TNF-α mRNA as well as IL-4 mRNA expression. In vitro, tofacitinib repressed the degranulation and cytokine production in RBL-2H3 cells and reduced histamine-induced vascular hyperpermeability. The underlying mechanism might involve the downregulation of phosphorylation of JAK3/STATs signaling molecules in RBL-2H3 cells and HUVECs.ConclusionsOur findings provide evidence that tofacitinib prevented EAC by targeting the JAK3/STATs pathway. We recommend the use of tofacitinib as an innovative approach for the treatment of AC.     

Anti-rheumatoid arthritis effects of flavonoids from Daphne genkwa

ObjectiveThis study aims to select the most effective anti-Rheumatoid Arthritis (RA) component of flavonoids from Daphne genkwa Sieb. et Zucc. by anti-inflammatory and immunomodulatory effects in vitro, and to elucidate the mechanism.MethodsThe anti-inflammatory and immunomodulatory effects of total flavonoids (TF) and four flavonoid components (genkwanin, hydroxygenkwanin, luteolin and apigenin) were determined by pharmacological approach in LPS-induced RAW 264.7 macrophages and ConA-induced T lymphocytes. Principal component analysis (PCA) was used to obtain the optimal anti-RA component in vitro. Western blot and real-time quantitative PCR (q-PCR) were used to explore the mechanisms. Finally, the in vitro anti-RA effect was verified by human rheumatoid arthritis fibroblast-like synoviocytes (FLSs).ResultsTF and four flavonoids significantly reduced the expressions of NO, iNOS, TNF-α, IL-6, IFN-γ and IL-2. PCA showed that genkwanin was the most effective anti-RA component in vitro. Genkwanin inhibited nuclear factor-κB (NF-κB) pathway by decreasing the phosphorylation levels of IKK, IκB and NF-κB, and down-regulated the expressions of iNOS, COX-2 and IL-6 mRNA. Genkwanin also inhibited the abnormal proliferation of FLSs and down-regulated the secretions of NO and IL-6.ConclusionThe most effective anti-RA component was genkwanin. Genkwanin exerts anti-RA effect through down-regulating the activation of NF-κB pathway and mRNA expressions of inflammatory mediators, and also by inhibiting the abnormal proliferation of FLSs and its NO and IL-6 secretion levels.     

Medicarpin prevents arthritis in post-menopausal conditions by arresting the expansion of TH17 cells and pro-inflammatory cytokines

Autoimmune diseases are characterized by alteration in balance of various cytokines. Rheumatoid arthritis is a well-known inflammatory disease leading to destruction of cartilage at knee and hands. Collagen-induced arthritis (CIA) is a common autoimmune model for rheumatoid arthritis study. Here, we have investigated the therapeutic role of medicarpin, a natural pterocarpan with known anti-osteoclastogenic activities, in postmenopausal polyarthritis model of DBA/1J mice. For this, mice were ovariectomized and CIA was induced in OVx animals with primary immunization. After 21 days, booster dose was injected in Ovariectomy (OVx) mice to develop postmenopausal poly-arthritis mice model. Medicarpin treatment in mice at dose of 10.0 mg/kg/body wt was started after 21 days of primary immunization for one month of time period every day orally. We found that medicarpin prevented alteration of TH-17/Treg ratio in CIA model leading to reduced osteoclastogenesis. Micro Computed Tomography (Micro-CT) analysis demonstrated that medicarpin prevents cartilage erosion in joints and restores loss of trabeculae parameters in distal tibia. Treatment with medicarpin also prevented alteration of various cytokines level by down-regulating various pro-inflammatory cytokines like TNF-α, IL-6 and IL-17A, while up-regulating anti-inflammatory cytokine IL-10 in CIA model of mice. Biological marker of arthritis is cartilage oligomeric matrix protein (COMP). COMP level was up-regulated in CIA induced mice while treatment with medicarpin significantly restored the serum level of COMP compared with untreated groups. Cartilage staining by Safranin-O also indicates that cartilage destruction in joints of CIA mice was prevented by medicarpin treatment. From this study, we can conclude that medicarpin is effective in preventing arthritis in post-menopausal conditions.     

3,4,5-Trihydroxycinnamic acid exerts a protective effect on pulmonary inflammation in an experimental animal model of COPD

3,4,5-Trihydroxycinnamic acid (THCA), a derivative of hydroxycinnamic acid, has been reported to exert anti-inflammatory and antioxidant activities. However, its anti-inflammatory effects in chronic obstructive pulmonary disease (COPD) have not yet been elucidated. Therefore, we explored the protective effects of THCA on pulmonary inflammation in an experimental COPD model elicited by cigarette smoke (CS) and lipopolysaccharide (LPS). Oral administration of THCA significantly inhibited the activity of elastase, the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO) and the numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) of experimental COPD mice. THCA also exerted inhibitory effects on the recruitment of inflammatory cells, the levels of PAS positive cells and cAMP-response-element-binding protein (CREB) activation, and the expression of phosphodiesterase 4 (PDE4) in the lungs of experimental COPD mice. In addition, THCA exerted a regulatory effect on the activation of p38, ERK and nuclear factor-κB (NF-κB) in the lungs of experimental COPD mice. THCA also significantly upregulated the expression of NAD(P)H dehydrogenase (quinone 1) 1 (NQO1) and the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) in the lungs of mice. Furthermore, THC restored the reduction of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in the lungs of experimental COPD mice. In phorbol myristate acetate (PMA)-stimulated A549 or H292 airway epithelial cells, pretreatment of THCA dose-dependently inhibited the generation of IL-6. THCA also led to increased NQO1 expression in H292 cells. Collectively, these protective effects of antioxidant THCA were notably excellent and are thought to be associated with the downregulation of MAPK (partial)/NF-κB signaling and upregulation of NQO1 and SIRT1 expression.     

Alendronate alleviates the symptoms of experimental autoimmune encephalomyelitis

Nitrogen-containing bisphosphonates, such as alendronate, have been widely used to treat osteoporosis because they may target multiple signals in the mevalonate cascade. The present study evaluated the therapeutic effects of alendronate on experimental autoimmune encephalomyelitis (EAE), which is a prototypical autoimmune disease model. EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG)_35-55 peptide. The mice were checked daily for clinical symptoms, such as paralysis, and the levels of inflammatory cytokines were analyzed using ELISA, western blot analyses, and immunohistochemistry. The daily oral administration of alendronate to EAE-induced mice significantly reduced the severity of paralysis and lowered T cell proliferation. Additionally, histopathological examinations confirmed that alendronate mitigated inflammation in the spinal cord after EAE induction, suppressed the infiltration of CD68-positive inflammatory cells, and reduced the production of various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, as well as inducible nitric oxide synthase (iNOS). Furthermore, the alendronate-treated group exhibited a decrease in the number of iNOS-positive inflammatory cells compared to the vehicle-treated group. Taken together, the present results suggest that alendronate alleviated neuro-inflammation in the spinal cords of EAE-induced mice, which is an animal model of multiple sclerosis, possibly by inhibiting the downstream effects of the mevalonate cascade.     

Empagliflozin attenuates neurodegeneration through antioxidant,anti-inflammatory,and modulation of α-synuclein and Parkin levels in rotenone-induced Parkinson’s disease in rats

Sodium-glucose co-transporter 2 (SGLT 2) inhibitors are a relatively new antidiabetic drug with antioxidant and anti-inflammatory properties. Therefore, this study aimed to investigate whether SGLT 2 inhibitors have a neuroprotective effect in PD. Twenty-four Wistar rats were randomized into four groups. The first one (control group) received dimethyl sulfoxide (DMSO) as a vehicle (0.2 mL/48 hr, S.C). The second group (positive control) received rotenone (ROT) (2.5 mg/kg/48 hr, S.C) for 20 successive days, whereas the third and fourth groups received empagliflozin (EMP) (1 and 2 mg/kg/day, orally), respectively. The two groups received rotenone (2.5 mg/kg/48 hr S.C) concomitantly with EMP for another 20 days on the fifth day. By the end of the experimental period, behavioral examinations were done. Subsequently, rats were sacrificed, blood samples and brain tissues were collected for analysis. ROT significantly elevated oxidative stress and proinflammatory markers as well as α-synuclein. However, dopamine (DP), antioxidants, tyrosine hydroxylase (TH), and Parkin were significantly decreased. Groups of (EMP + ROT) significantly maintained oxidative stress and inflammatory markers elevation, maintained α-synuclein and Parkin levels, and elevated TH activity and dopamine level. In both low and high doses, EMP produced a neuroprotective effect against the PD rat model, with the high dose inducing a more significant effect.     

Isofraxidin ameliorated influenza viral inflammation in rodents via inhibiting platelet aggregation

Platelets have been proved to exacerbate influenza infection and its complications. Inhibition of platelet activation may be a feasible method for preventing severe infection and secondary acute lung injury (ALI). Isofraxidin (IFD) is a natural coumarin isolated from the plants Sarcandra glabra and Siberian ginseng, and exerts anticancer, antioxidant and antiinflammatory effects. In the present study, we examined the therapeutic effects of IFD in ADP- or arachidonic acid (AA)-induced platelet aggregation model and in influenza A virus (IAV)-induced ALI mouse model. The results showed that IFD significantly inhibited platelet aggregation induced by ADP and AA in vitro in a concentration-dependent manner as well as the release of soluble P-selectin and platelet factor 4. Moreover, IFD significantly relieved IAV-induced lung inflammation, reduced the expressions of platelet activation biomarkers (P-selectin and CD61), decreased the serum levels of TNF-α, IL-1β, IL-6 and MIP-2, suppressed peripheral platelet aggregation and prolonged the survival time of infected mice. The western blotting results also demonstrated that IFD reduced the phosphorylation levels of PI3K, AKT and p38 in the activated platelets stimulated by ADP and IAV infection. But IFD did not have any effects on IAV replication. It indicated that IFD ameliorated IAV-induced severe lung damage and lethal infection by suppressing platelet aggregation via regulating PI3K/AKT and MAPK pathways.     

UFL1 attenuates IL-1β-induced inflammatory response in human osteoarthritis chondrocytes

Osteoarthritis (OA) is a chronic inflammatory joint disease characterized by degradation of articular cartilage. Ubiquitin-fold modifier 1 (UFM1)-specific ligase 1 (UFL1) is an UFM1 E3 ligase that has been identified as a regulator of inflammatory response. However, the role of UFL1 in OA remains unknown. The aim of the present study was to explore the function of UFL1 in an in vitro OA system in chondrocytes. Our results showed that UFL1 was lowly expressed in both OA articular tissues and chondrocytes with IL-1β induction. Ectopic expression of UFL1 improved cell viability of IL-1β-induced chondrocytes. UFL1 suppressed the production of NO and PGE2, as well the expression levels of iNOS and COX-2 in IL-1β-induced chondrocytes. The IL-1β-induced increases in TNF-α and IL-6 levels were attenuated by UFL1. Ectopic expression of UFL1 inhibited the production of extracellular matrix (ECM) degrading enzymes including matrix metalloproteinase 3 (MMP-3), MMP-13, ADAMTS-4 and ADAMTS-5 in chondrocytes with IL-1β induction. Additionally, UFL1 suppressed IL-1β-induced activation of NF-κB signaling pathway in chondrocytes. In conclusion, these findings indicated that UFL1 exerted protective effect on IL-1β-induced chondrocytes. Thus, UFL1 might be a potential target for the treatment of OA.     

Secoisolariciresinol diglucoside suppresses Dextran sulfate sodium salt-induced colitis through inhibiting NLRP1 inflammasome

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal inflammatory disease with high risks for colorectal cancer and extremely affect people's health. Secoisolariciresinol diglucoside (SDG), a major component of lignans, exerts anti-inflammatory effects against digestive system diseases through a multi-target mechanism. However, the effect of SDG on IBD is not clear. In the present study, we aimed to investigate the effects of SDG on IBD and elucidate the underlying mechanism. The Dextran Sulfate Sodium Salt (DSS)-induced colitis model and lipopolysaccharide (LPS) stimulated RAW264.7 mouse macrophages cellular inflammation model were established. Morphological and pathological changes in colitis tissue in mice were observed by HE staining. Macrophage infiltration was detected by flow cytometry. The levels of nucleotide oligomerization domain-like receptor protein 1 (NLRP1) inflammasome complexes, nuclear factor-kappa B (NF-κB) and inflammatory cytokines were determined using quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The results showed that SDG significantly attenuated the pathological severity and the number of macrophage infiltration of colitis in mice. Besides, SDG decreased the levels of inflammatory cytokines (IL-1β, IL-18 and TNF-α) and inhibited the activation of the NLRP1 inflammasome in DSS-induced colitis mice and RAW264.7 mouse macrophages. Moreover, the inhibitory effect of SDG was partly dependent on the disruption of NF-κB activation. Our results indicated that SDG relieves colitis by inhibiting NLRP1 inflammasome, and partly dependent on the disruption of NF-κB activation. Therefore, SDG may be a potential treatment option for IBD.     

Dexmedetomidine inhibits the invasion,migration, and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by reducing the expression of NLRC5

Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by inflammatory synovitis, but its pathogenesis remains unclear. NLRC5 is a newly discovered member of the NLR family that is effective in regulating autoimmunity, inflammatory responses, and cell death processes. Dexmedetomidine (DEX) has been reported to have a variety of pharmacological effects, including anti-inflammatory and analgesic effects. However, the role of DEX in RA has not been explored. In adjuvant-induced arthritis (AA) rat models, DEX (10 μg/kg and 20 μg/kg) reduced the pathological score, the arthritis score, paw swelling volume, and the serum levels of IL-1β, IL-6, IL-17A, and TNF-α. Moreover, by using Western blot and real-time quantitative PCR (RT-qPCR), it was demonstrated that DEX can inhibit the expression of IL-1β, IL-6, MMP-3, MMP-9 and P-P65 in the synovial tissue of AA rats. In human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), DEX (250 nM and 500 nM) was found to inhibit the expression of IL-1β, IL-6, MMP-3, MMP-9, and P-P65 following stimulation with TNF-α. Moreover, DEX can inhibit the invasion and migration of RA-FLSs stimulated by TNF-α. Finally, the expression of NLRC5 in RA-FLSs and AA rat models was also reduced by DEX. After silencing NLRC5 in RA-FLSs, the expression of IL-1β, IL-6, MMP-3, MMP-9, and P-P65, as well as the invasion and migration of cells, were significantly reduced. These results indicate that DEX inhibits the invasion, migration, and inflammation of RA-FLSs by reducing the expression of NLRC5 and inhibiting the NF-κB activation.     

Nano-curcumin therapy,a promising method in modulating inflammatory cytokines in COVID-19 patients

BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery.     

The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo

Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.