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Assessment of the involvement of the macrophage migration inhibitory factor–glucocorticoid regulatory dyad in the expression of matrix metalloproteinase‐2 during periodontitis 下载免费PDF全文
Josefine Hirschfeld Mohammed Howait Alexandru Movila Marijo Parčina Isabelle Bekeredjian‐Ding James Deschner Søren Jepsen Toshihisa Kawai 《European journal of oral sciences》2017,125(5):345-354
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and counter‐regulator of endogenous glucocorticoids (GCs). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF–GC regulatory dyad in the expression and release of matrix metalloproteinase‐2 (MMP‐2) during periodontitis, in vivo and in vitro. In a Mif‐knockout (KO) mouse model of ligature‐induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin‐6 (IL‐6), MIF, MMP‐2, and corticosterone. In addition, human gingival fibroblasts (HGFs) were tested for production of IL‐6 and MMP‐2 after stimulation with hydrocortisone (HC), MIF, tumour necrosis factor‐alpha (TNF‐α), or Fusobacterium nucleatum, a pathogen known to elicit immune responses during periodontitis. Wild‐type (WT) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL‐6 concentrations. Systemic GC levels were reduced in WT and Mif‐KO mice during inflammation, with overall lower concentrations in Mif‐KO mice. In vivo and in vitro, MMP‐2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC. Therefore, MIF does not appear to stimulate expression of MMP‐2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP‐2. Our findings further suggest that MIF may regulate systemic GC levels. 相似文献
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Dan Domocos Tudor Selescu Laura Cristina Ceafalan Mirela Iodi Carstens Earl Carstens Alexandru Babes 《Journal of neuroscience research》2020,98(10):1999-2017
Serotonin (5-hydroxytryptamine, 5-HT) released by platelets, mast cells, and immunocytes is a potent inflammatory mediator which modulates pain and itch sensing in the peripheral nervous system. The serotonergic receptors expressed by primary afferent neurons involved in these sensory functions are not fully identified and appear to be to a large extent species dependent. Moreover, the mechanisms through which 5-HT receptor activation is coupled to changes in neuronal excitability have not been completely revealed. Using a combination of in vitro (calcium and voltage imaging and patch-clamp) and in vivo behavioral methods, we used both male and female Wistar rats to provide evidence for the involvement of two 5-HT receptor subtypes, 5-HT1A and 5-HT3, in mediating the sustained and transient effects, respectively, of 5-HT on rat primary afferent neurons involved in pain and itch processing. In addition, our results are consistent with a model in which sustained serotonergic responses triggered via the 5-HT1A receptor are due to closure of background potassium channels, followed by membrane depolarization and action potentials, during which the activation of voltage-gated calcium channels leads to calcium entry. Our results may provide a better understanding of mammalian serotonergic itch signaling. 相似文献
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A new comprehensive 12‐segment approach to right ventricular systolic and diastolic functions by 2D speckle tracking echocardiography in healthy individuals 下载免费PDF全文
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Introduction:Mycoplasma pneumoniae (MP) infection in infants is usually overlooked and it might result in important complications if left untreated. MP-induced arthritis is probably the least common extrapulmonary manifestation and frequently leads to delays in the diagnosis.Patient concerns:We report the case of a 2-year-old female child admitted in our clinic for prolonged fever (onset 2 weeks before the admission), for which the general practitioner established the diagnosis of acute pharyngitis and recommended antibiotics. But the fever persisted and the patient was referred to a pediatrician.Diagnosis:The laboratory tests revealed leukocytosis with neutrophilia, elevated C-reactive protein and liver cytolysis. The blood and urine cultures, as well as the serological hepatitis B and C, toxoplasmosis, Epstein Barr virus, Rubella, Herpes virus, and cytomegalovirus were negative. The chest X-ray established the diagnosis of pneumonia. The fever persisted for approximately 2 weeks after admission. On the 2nd week of admission, the patient began to experience gait difficulties complaining of pain in the right hip and ankle. The cardiology and pneumology consults revealed no pathological findings. The evolution was favorable after the initiation of Levofloxacin and MP infection was detected as we suspected. Moreover, the ultrasound of the hip revealed a mild joint effusion, while the ankle joint appeared to be normal at ultrasound. Thus, we established the diagnosis of hip and ankle arthritis based on the clinical and ultrasound findings.Interventions:Levofloxacin by vein was continued for 5 days, replaced afterwards with clarithromycin orally for 2 weeks.Outcomes:The gait difficulties persisted for approximately 5 months from the initial diagnosis, and improved once the titer of immunoglobulin M anti-MP antibodies lowered considerably. After more than 8 months, the patient was completely asymptomatic and the immunoglobulin M anti-MP was close to the normal range.Conclusion:The awareness of MP-induced arthritis in children represents the cornerstone in preventing diagnostic delays and initiating the proper treatment. 相似文献