Multiplex analysis of cytokines, chemokines, growth factors, MMP-9 and TIMP-1 produced by human bone marrow, adipose tissue, and placental mesenchymal stromal cells

Comparative analysis of mesenchymal stromal cells isolated from human BM, adipose tissue, and placenta was carried out. The cells were compared by the levels of constitutive, spontaneous, and LPS-induced production of Th1/proinflammatory (IFN-γ, IL-2, IL-1β, TNF-α, IL-12, IL-17) and Th2/anti-inflammatory cytokines (IL-4, IL-5, IL-6, IL-10, IL-13), chemokines (IL-8, MCP-1, MIP-1β), growth factors (IL-7, granulocytic CSF, granulocytic macrophageal CSF, erythropoietin, VEGF, EGF, IGF-1, main FGF), matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Mesenchymal stromal cells originating from different tissues were characterized by functional potential for hemopoiesis support (through production of granulocytic CSF, granulocytic macrophage CSF, erythropoietin), immunomodulation (through production of IFN-γ, IL-2, IL-6, IL-1β, TNF-α and chemokines IL-8, MCP-1, MIP-1β), and stimulation of reparative processes (through production of VEGF, FGF, IGF-1, IL-6 tissue inhibitor of metalloproteinase-1, and matrix metalloproteinase-9). By the type and levels of spontaneous (basal) production of cytokines, the adipose tissue mesenchymal stromal cells more distinctly demonstrated the proinflammatory (IL-1β TNF-α), immunoregulatory (IFN-γ, IL-2, IL-4, IL-6, IL-8, MCP-1, MIP-1β), and hemopoiesis-stimulating (granulocytic CSF, granulocytic macrophage CSF) phenotype and at the same time were characterized by lower sensitivity to lipopolysaccharide stimulation than BM and placental mesenchymal cells.     

Few differences in cytokines between patients newly diagnosed with type 1 diabetes and their healthy siblings

The cause of the worldwide increase in type 1 diabetes (T1D) is largely unknown. T cells are thought to play a role in disease progression. In contemporary research over the last decade, age- and gender-specific serum levels as well as changes of Th1 and Th2-related cytokines are not well described. From a population-based register of children diagnosed from 1997 to 2005 this study explores eight different cytokines at time of diagnosis. Only TGF-β and IL-18 showed higher levels in patients compared to siblings in an adjusted model (p < 0.01); whereas the other seven cytokines were not significantly different. IL-1β, IL-18, IL-12, IL-10 and IL-4 were significantly higher among the youngest children and males had significantly lower levels of IL-10 and IL-12 but higher levels of TNF-α. During the nine-year study all of the cytokines increased except TGF-β, which showed a slight decrease over time. The cytokine levels tended to be highest during summer and were most pronounced for IL-1β and TNF-α. In conclusion, serum levels of known β-cell cytotoxic cytokines were indifferent in patients and siblings, while gender, age and season appear to exert some influence on the serum level and need to be explored further. The influence of time on systemic levels cannot be ignored and may reflect decay or environmental impact on the immune system.     

大鼠胰岛β细胞损伤中IL-18的作用研究

新生Wistar大鼠离体胰岛与细胞因子孵育后 ,观测胰岛素释放和一氧化氮 (NO )生成的变化 ,并用逆转录 聚合酶链反应 (RT PCR )观察IL 18受体信号链 (IL 18Rβ )mRNA的表达水平。结果表明 :(1) 0 6 2 5～ 10nmol/L基因重组小鼠 (rm )IL 18孵育胰岛 2 4h后 ,对累积的和葡萄糖刺激的胰岛素释放以及NO生成均无显著效应 ;(2 ) 2 0 0U/ml基因重组大鼠 (rr)γ干扰素 (IFN γ )或 2 5 0U/ml基因重组人 (rh )肿瘤坏死因子 α (TNF α)单独存在对胰岛素释放和NO生成均无明显效应 ,也不能促使 10nmol/LrmIL 18对胰岛素释放和NO生成产生影响 ;(3) 2 0 0U/mlrrIFN γ +2 5 0U/mlrhTNF α或 15pg/mlrhIL 1β均明显促进NO生成和抑制胰岛素释放 ,而 10nmol/LrmIL 18则不影响IFN γ +TNF α或IL 1β的上述效应 ;(4 )即使经IL 1β和 (或 )IFN γ +TNF α或IL 12孵育后 ,大鼠胰岛素瘤 (RIN )细胞或离体大鼠胰岛仍未见IL 18RβmRNA的表达。提示IL 18在细胞因子所致胰岛β细胞损伤中不发挥直接作用 ,原因是IL 18受体在胰岛 β细胞中不表达。     

Selective regulation of ICAM-1 and major histocompatibility complex class I and II molecule expression on epidermal Langerhans cells by some of the cytokines released by keratinocytes and T cells

Epidermal Langerhans cells (LC) are major histocompatibility complex (MHC) class II (Ia)-positive dendritic cells that act as potent antigen-presenting or accessory cells for primary and secondary T cell-dependent immune responses. Recent studies have disclosed that the morphological, functional, and phenotypic characteristics of LC are variably and drastically modulated by external stimuli both in vivo and in vitro. However, little is known of the biological significance of diverse cytokines in regulating the surface molecules of LC. To determine the regulatory properties of ICAM-1, Ia, and MHC class I (H-2K) molecules in LC, we have examined the effects of interleukin (IL)-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-10, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the expression of these molecules. Among the cytokines examined, IFN-γ markedly and reproducibly up-regulates the expression of H-2K, but not ICAM-1, in Ia⁺ LC in a time- and dose-dependent manner. TNF-α consistently up-regulates the expression of ICAM-1, but not H-2K, in a time- and dose-dependent manner. IL-10 slightly but reproducibly inhibits the expression of ICAM-1, but not H-2K, in a time- and dose-dependent manner. IL-10 potently inhibits the TNF-α-induced ICAM-1 up-regulation, but not the IFN-γ-induced H-2K up-regulation. Moreover, no cytokine consistently affects the Ia expression of LC. In addition, slight enhancing effects have been observed on H-2K expression by IL-4, and on ICAM-1 expression by IL-1α, IL-1β, or GM-CSF. The present data suggest that the selective regulation is operative in a certain cell surface moiety of LC by various cytokines. These results further facilitate our understanding of immunobiology of LC.     

IL-27, targeting antigen-presenting cells,promotes Th17 differentiation and colitis in mice

T helper type 17 (Th17) cells have been implicated in autoimmunity and inflammatory bowel disease (IBD). Antigen-presenting cell (APC) -derived cytokines such as interleukin (IL)-1β and IL-6 are key mediators supporting Th17 differentiation, yet how these factors are induced in vivo remains unclear. Here, we show that IL-27 acting on APCs enhances IL-6 and IL-1β production and Th17 differentiation. IL-27Rα−/− T-cell receptor (TCR)β−/− recipients fail to develop gut inflammation following naive CD4 T-cell transfer, whereas IL-27Rα+/+ TCRβ−/− recipients develop severe colitis. Investigation of T-cell responses exhibits that IL-27Rα−/− TCRβ−/− mice do not support Th17 differentiation with significantly decreased levels of IL-6 and IL-1β by APCs. Our study has identified a novel proinflammatory role for IL-27 in vivo that promotes Th17 differentiation by inducing Th17-supporting cytokines in APCs.     

Increasing proliferation of murine adipose tissue-derived mesenchymal stem cells by TNF-α plus IFN-γ

The objective of the current study was to assess the effects of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) along with their simultaneous application on proliferation and pluripotency genes of murine adipose tissue-derived mesenchymal stem cells (AT-MSCs). The proliferation, doubling time (DT), colony-forming unit–fibroblast (CFU-F), pluripotency genes expression, and proliferation-related immunomodulatory markers of MSCs were analyzed upon activation with TNF-α (10?ng/ml), IFN-γ (10?ng/ml) and both TNF-α and IFN-γ (5?ng/ml?+?5?ng/ml). Pluripotency genes including Oct-4, Sox-2, and Nanog as well as proliferation-associated immunomodulatory cytokines such as insulin-like growth factor 1 (IGF-1) and transforming growth factor-β (TGF-β) expression were evaluated using real-time PCR. Surface expression of Qa2 (HLA-G) was analyzed by flow cytometry. Pretreatment of MSCs with TNF-α plus IFN-γ led to significantly increased proliferation, DT and CFU-F as well as expression of pluripotency genes in AT-MSCs (p < 0.01). MSCs expressed more IGF-1, TGF-β, and Qa2 upon activation with TNF-α plus IFN-γ and IFN-γ. MSCs expressed significantly decreased amounts of TGF-β and Qa2 in presence of TNF-α. TNF-α combined with IFN-γ may be improved the proliferation of AT-MSCs. Conversely, expanded MSCs pointed out low levels of the immunomodulatory marker, s especially Qa2 in the presence of TNF-α. In conclusion, we showed that TNF-α together with IFN-γ increased the proliferation of MSCs and slightly enhanced the expression of pluripotency genes.     

TNF-α and IL-1β sensitize human MSC for IFN-γ signaling and enhance neutrophil recruitment

During inflammatory processes, tissue environmental cues are influencing the immunoregulatory properties of tissue-resident mesenchymal stem/stromal cells (MSC). In this study, we elucidated one of the molecular and cellular responses of human MSC exposed to combinations of inflammatory cytokines. We showed that during multi-cytokine priming by TNF-α, IL-1β, and IFN-γ, IL-1β further augmented the well-established immunoregulatory activity induced by TNF-α/IFN-γ. On the molecular level, TNF-α and IL-1β enhanced the expression of IFN-γ receptor (IFN-γR) via NF 'kappa-light-chain-enhancer' of activated B-cells (NF-κΒ) signaling. In turn, enhanced responsiveness to IFN-γ stimulation activated STAT5 and p38-MAPK signaling. This molecular feedback resulted in an increased IL-8 release and augmented recruitment of polymorphonuclear granulocytes (PMN). Our study suggests the possibility that responses of MSC to multi-cytokine priming regimens may be exploited therapeutically to fine-tune inflammatory activity in tissues. This study elucidates molecular mechanisms underlying the immunological priming of mesenchymal stromal cells (MSC) and their interaction with neutrophils.     

EXPRESSION OF VASCULAR CELL ADHESION MOLECULE-1 IN MURINE HEARTS WITH ACUTE MYOCARDITIS CAUSED BY COXSACKIEVIRUS B3

Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of the myocardial cell damage involved in viral myocarditis. Using a murine model of acute myocarditis caused by Coxsackievirus B3 (CVB3), perforin-expressing killer cells have been shown to infiltrate the heart, and intercellular adhesion molecular-1 (ICAM-1) together with major histocompatibility complex (MHC) antigen was induced on myocardial cells in acute viral myocarditis. To clarify the immunological mechanisms in more detail, the expression of vascular cell adhesion molecular-1 (VCAM-1) has been examined in the heart of acute myocarditis and on cultured cardiac myocytes treated with interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). The effects of in vivo antibody treatment to VCAM-1 on myocardial damage involved in acute myocarditis were also analysed. CVB3-induced myocarditis resulted in enhanced expression of VCAM-1 on myocardial cells. VCAM-1 expression was also induced on cultured cardiac myocytes by treatment with IFN-γ and TNF-α. The in vivo antibody treatment to VCAM-1 decreased the myocardial damage to some extent, but the effects were not statistically significant. These data suggest that the expression of VCAM-1 on myocardial cells may play at least a partial role in the myocardial damage involved in acute viral myocarditis.     

Retinal ganglion cell death is induced by microglia derived pro-inflammatory cytokines in the hypoxic neonatal retina

Hypoxic injury, including that resulting in the retinopathy of prematurity, may induce retinal ganglion cell (RGC) death in the neonatal retina. We hypothesized that this may be mediated by excess production of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) by microglia. One-day-old Wistar rats were subjected to hypoxia for 2 h and the expression of TNF-α and IL-1β and their receptors was determined in the retina. The mRNA and protein expression of TNF-α, IL-1β, TNF-receptor 1 (TNF-R(1)), and IL-1 receptor 1 (IL-1R(1)) and the tissue concentration of TNF-α and IL-1β were up-regulated significantly after the hypoxic exposure. TNF-α and IL-1β immunoreactivity was localized in microglial cells, whereas that of TNF-R(1) and IL-1R(1) was restricted to RGCs, as confirmed by double immunofluorescence labelling. Along with this, increased expression of monocyte chemoattractant protein-1 and its receptor CCR2 was detected in the microglia. Primary cultured microglia subjected to hypoxia showed enhanced release of TNF-α and IL-1β. Primary cultured retinal ganglion cells (RGCs) treated with conditioned medium derived from hypoxic microglia showed enhanced apoptosis, which was significantly reduced when the cells were treated with microglia conditioned medium neutralized with TNF-α/IL-1β antibody. Our results suggest that activated microglial cells in hypoxic neonatal retina produce increased amounts of TNF-α and IL-1β that could induce RGC death.     

Expression of macrophage inflammatory protein (MIP)-1α, MIP-1β, and RANTES genes in lymph nodes from HIV+ individuals: correlation with a Th1-type cytokine response

The in vivo response of the immune system after HIV infection in regard to cytokine production and C-C chemokine synthesis is not well known. Here we have analysed cytokine and chemokine mRNA production in lymph nodes with follicular hyperplasia (FHLN) of HIV-infected patients by in situ hybridization using anti-sense mRNA probes. The synthesis of mRNAs for interferon-gamma (IFN-γ), IL-12p35, IL-12p40, IL-4, and for the C-C chemokines RANTES, MIP-1α, and MIP-1β was compared with that of lymph nodes from non-infected individuals to define HIV-specific events. Only few cells expressing IFN-γ, RANTES, MIP-1α, and MIP-1β mRNAs were detectable in the T-dependent area of lymph nodes from HIV-negatives. In contrast, in FHLN from HIV⁺ patients a high number of IFN-γ, RANTES, MIP-1α, and MIP-1β mRNA-containing cells were detectable. Remarkably, only single individual IL-12p35 mRNA-producing cells were present in the T-dependent area from both HIV⁺ and HIV^? lymph nodes. Furthermore, the low number of IL-12p40 mRNA-expressing cells did not differ between HIV⁺ and HIV^? lymph nodes. This indicates that IFN-γ is expressed independently of IL-12, possibly by a direct T cell-mediated reaction. IL-4 mRNA-producing cells were hardly detectable in infected and control lymph nodes. The same findings were made in a limited number of samples from patients with advanced disease. Thus, these results demonstrate that a high IFN-γ production is accompanied by a strong expression of MIP-1α, MIP-1β, and RANTES in the lymph node after HIV infection. This favours the idea that a Th1-type immune response correlates with a preferential production of C-C chemokines in FHLN of HIV⁺ patients.     

IL4-10 fusion protein: a novel immunoregulatory drug combining activities of interleukin 4 and interleukin 10

The objective of this study was to test the capacity of a newly developed fusion protein of interleukin 4 (IL-4) and IL-10 [IL4-10 fusion protein (FP)] to shift multiple pro-inflammatory pathways towards immune regulation, and to inhibit pro-inflammatory activity in arthritis models. The effects of IL4-10 FP in comparison with IL-4, IL-10 and IL-4 plus IL-10 on pro- and anti-inflammatory mediators, T cells and immunoglobulin (Ig) receptors in favour of immunoregulatory activity were studied. In addition, the capacity of IL4-10 FP to inhibit pro-inflammatory activity in ex-vivo and in-vivo arthritis models was investigated. IL4-10 FP robustly inhibited pro-inflammatory cytokine [IL-1β, tumour necrosis factor (TNF)-α, IL-6 and IL-8] production in whole blood cultures, mediated by both the IL-10 and the IL-4 moiety. IL4-10 fusion protein induced IL-1 receptor antagonist (IL-1RA) production and preserved soluble TNF receptor (sTNFR) levels, strongly increasing IL-1RA/IL-1β and sTNFR/TNF-α ratios. In addition, IL4-10 FP strongly inhibited T helper (Th) type 1 and 17 cytokine secretion, while maintaining FoxP3 expression and up-regulating Th2 activity. In addition, while largely leaving expression of activating Fc gamma receptor (FcγR)I, III and Fc epsilon receptor (FcεR) unaffected, it significantly shifted the FcγRIIa/FcγRIIb ratio in favour of the inhibitory FcγRIIb. Moreover, IL4–10 FP robustly inhibited secretion of pro-inflammatory cytokines by rheumatoid arthritis synovial tissue and suppressed experimental arthritis in mice, without inducing B cell hyperactivity. IL4-10 fusion protein is a novel drug, signalling cells to induce immunoregulatory activity that overcomes limitations of IL-4 and IL-10 stand-alone therapy, and therefore has therapeutic potential for inflammatory diseases such as rheumatoid arthritis.     

Evidence for Cytokine Dysregulation in Multiple Sclerosis: Peripheral Blood Mononuclear Cell Production of Pro-inflammatory and Anti-inflammatory Cytokines During Relapse and Remission

We investigated circulating anti-inflammatory and pro-inflammatory cytokines, and their ex vivo PBMC production in the absence or presence of the neuroantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) and T cell mitogen (PHA) in MS patients in relapse and remission, patients with other neurological disorders (OND) and normal healthy controls. MS patients in relapse exhibited significantly increased PBMC production of TNF-α spontaneously compared with MS remission and healthy controls and with MBP compared with MS remission. Patients in relapse had significantly increased spontaneous, PHA- and MBP-induced PBMC IL-1β production compared with remission MS, and was increased compared (PHA only) with OND and healthy controls. In relapse there was also significantly increased PBMC IFN-γ production (PHA only) compared with remission and a significantly lower production of biologically active TGF-β1 (PHA only) compared with remission MS and OND. In contrast, MS patients in remission produced significantly less spontaneous and MBP-induced TNF-α, spontaneous, PHA- and MBP-induced IL-1β and PHA-induced IFN-γ together with increased production of biologically active TGF-β1. MOG non-specifically increased PBMC TNF-α and IL-1β production in all groups. Pro-inflammatory cytokines in corresponding plasma samples were undetectable whilst the concentration of biologically active TGF-β1 was the reverse of ex vivo PBMC findings. The increase in biologically active TGF-β1 production ex vivo in OND patients, despite active disease, compared with the low level in the MS relapse may indicate a regulatory defect in MS. We conclude that the balance between biologically active TGF-β1 and the pro-inflammatory TNF-α, IL-1β and IFN-γ is dysregulated during MS relapse-remission and that normal counter-regulatory mechanisms during the relapse phase are defective.     

TH1/TH2细胞因子与习惯性流产的关系研究

目的通过测定习惯性流产患者（RSA）及正常妊娠妇女外周血血清TH1/TH2细胞因子的含量,探讨TH1/TH2细胞因子与习惯性流产发生的关系。方法采用酶联免疫吸附法检测30例RSA患者,72例正常妊娠妇女血清IL-2、IL-4、IL-10、IFN-γ、TNF-α及TNF-β水平并比较两组之间的差异。结果RSA患者IL-2、IL-4、IL-10、IFN-γ、TNF-α血清水平显著高于正常妊娠妇女（P〈0.05）,TNF-β血清水平显著低于正常妊娠妇女（P〈0.05）。结论血清IL-2、IL-4、IL-10、IFN-γ、TNF-α水平可能在习惯性流产发生中起重要作用。     

IL-4, IL-10 and IL-13 down-regulate monocyte-chemoattracting protein-1 (MCP-1) production in activated intestinal epithelial cells

Several studies have demonstrated that intestinal epithelial cells play a major role in the initiation and perpetuation of intestinal inflammation by secreting proinflammatory cytokines and chemokines. MCP-1 is suggested to be a chemokine that plays a major part during intestinal inflammation in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4, IL-10 and IL-13 have been described to exert anti-inflammatory properties on various cell types. The aim of our study was to determine the effect of Th2 cytokines on the production of MCP-1 by activated intestinal epithelial cells. We examined Caco-2 cells as well as intestinal epithelial cells which were isolated from surgical specimens. Production of the chemokine MCP-1 was determined under stimulated and non-stimulated conditions. IL-4, IL-10 and IL-13 were added to stimulated epithelial cells under various culture conditions. Supernatants were analysed for cytokine concentrations using ELISAs. Under stimulation with physiological agents like IL-1β or tumour necrosis factor-alpha (TNF-α), we observed markedly increased concentrations of MCP-1 in supernatants of Caco-2 cells and intestinal epithelial cells. IL-4, IL-10 and IL-13 all had the capacity to down-regulate the production of MCP-1 in Caco-2 cells as well as in freshly isolated epithelial cells. Caco-2 cells which were primed with Th2 cytokines 24 h before stimulation were subsequently decreased in their ability to be stimulated by IL-1β or TNF-α for MCP-1 production. As MCP-1 has been shown to play a major role during intestinal inflammation, the in vitro suppression of MCP-1 in enterocytes suggests the in vivo use of regulatory cytokines in patients with active IBD.     

Characterization of cytokine production in murine Trypanosoma cruzi infection by in situ immunocytochemistry: Lack of association between susceptibility and type 2 cytokine production

Cytokine production in the spleens of mice infected with the protozoan parasite Trypanosoma cruzi was analyzed in three models which differ in the outcome of the infection. Using immunocytochemical techniques to detect cytokine-producing cells, the production of type 1 [interleukin-2 (IL-2) and interferon (IFN)-γ], type 2 (IL-4, IL-5, IL-10), inflammatory [tumor necrosis factor (TNF)-α, IL-1α, IL-6] and regulatory (transforming growth factor-β) cytokines were examined. With the exception of IL-4 and IL-5, cells producing all of the cytokines assayed were detected in both the resistant and susceptible models of T. cruzi infection. Cells producing IL-4 and IL-5 were not detected until later in infection in the resistant mice (>34 days), at about the time animals of the susceptible strain succumb to the infection. Mice of the susceptible model showed a slight delay in the appearance of cells producing the type 1 cytokines IL-2 and IFN-γ and an earlier appearance of TNF-producing cells, in comparison to resistant mice. Cells producing IL-2 or IL-10 were transient in their appearance in the spleen while cells producing IL-1, IL-4, IL-5, IL-6, IFN-γ, TNF, or TGF-β were first detectable in either the acute or post-acute stage of the infection and persisted up to 700 days post infection in two different resistant models of the infection. Cells producing IFN-γ, TNF-α and TGF-β were particularly numerous even very late in the infection. Double-staining techniques were used to show that the vast majority of the IFN-γ-producing cells in the spleen were CD4^?, CD8^? α/β TCR⁺ T cells. This study confirms the transience of IL-2 production in the acute stage of T. cruzi infection and the persistent and simultaneous production of type 1 and type 2 cytokines during the late-acute and chronic stages of the infection. Susceptibility or resistance to T. cruzi infection does not associate with a Th2 pattern of cytokine production in the three models examined in this study. The overlapping pattern of type 1 and type 2 cytokine-producing cells in both the acute and chronic stages of T. cruzi infection demonstrates that longterm infections do not necessarily lead to a dominance of either type 1 or type 2 cytokine production.     

Lactobacillus plantarum C29 alleviates NF-κB activation and Th17/Treg imbalance in mice with TNBS-induced colitis

In this study, we examined whether Lactobacillus plantarum C29 could restore 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced T helper 17 (Th17)/regulatory T cells (Tregs) imbalance in mice. Treatment with C29 inhibited the differentiation of splenic T cells into Th17 cells and the expression of retinoic acid receptor-related orphan receptor gamma t (RORγt) and IL-17 in vitro, whereas promoting the differentiation into Tregs. Oral administration of Lactobacillus plantarum C29 in mice attenuated TNBS-induced colon shortening, myeloperoxidase (MPO) activity, inducible Nitric oxide (NO) synthase, and cyclooxygenase-2 expression, and activation of NF-κB in the colon of mice. C29 treatment downregulated TNF-α, IL-17, and IL-1β expression, while increasing IL-10 expression. C29 treatment suppressed TNBS-induced Th17 cell differentiation and reduced IL-17 and RORγt expression, while promoting the TNBS-suppressed Tregs differentiation and IL-10 and forkhead box P3 expression. These findings suggest that C29 can alleviate colitis by modulating NF-κB activation as well as Th17/Treg balance.