IL6 peptide

Periodontitis is a chronic inflammatory disease of the gum caused by infection with multispecies oral bacteria. Since the periodontopathic bacteria, Porphyromonas gingivalis together with Enterococcus faecalis are frequently detected in patients with a severe form of periodontitis, interactions between their virulence factors might play an important role in progression of the disease. P. gingivalis and E. faecalis possess lipopolysaccharide (Pg.LPS) and lipoteichoic acid (Ef.LTA), respectively, as the major virulence factors inducing inflammatory responses. However, the combinatorial effect of these virulence factors on chemokine expression was poorly understood. Here, we examined the interaction between Ef.LTA and Pg.LPS on IL-8 induction in human periodontal ligament (PDL) cells. Pg.LPS, but not Ef.LTA, induced IL-8 expression at both mRNA and protein levels, which was suppressed in the presence of Ef.LTA. Although Ef.LTA and Pg.LPS could stimulate Toll-like receptor 2 (TLR2), Ef.LTA did not interfere with Pg.LPS induced-TLR2 activation. However, Ef.LTA decreased Pg.LPS-induced phosphorylation of ERK, JNK, and p38 kinase. Furthermore, Ef.LTA suppressed Pg.LPS-induced IL-8 promoter activity as well as AP-1, NF-IL6 and NF-kappa B transcription factors, which are indispensable for IL-8 expression. Interestingly, Ef.LTA enhanced only IL-1 receptor-associated kinase-M (IRAK-M) expression among the tested negative regulators of TLR intracellular signaling cascades in the presence of Pg.LPS. In addition, silencing IRAK-M restored the decreased IL-8 expression by Ef.LTA in the presence of Pg.LPS. Collectively, these results suggest that Ef.LTA inhibits Pg.LPS-induced IL-8 expression in human PDL cells via inducing the expression of a negative regulator of TLR signaling cascades, IRAK-M.

Problem. Some G-protein-coupled receptors (GPCRs) are regulators of inflammation, yet the role of the GPRC, GPR91, is unknown in human myometrium during the processes of human labor and delivery, a major inflammatory event. Method of Study. GPR91 mRNA expression was assessed using RT-qPCR in myometrium obtained from women at term Caesarean section in the absence of labor and during active spontaneous labor and in a mouse model of inflammation-induced preterm labor. Human primary myometrial cells were used to determine the effect of proinflammatory mediators on GPR91 and the effect of GPR91 siRNA on prolabor mediators. Statistical significance was ascribed to a P<0.05. Results. GPR91 mRNA expression was significantly higher in myometrium from women during term spontaneous labor compared to no labor. Likewise, in mice, GPR91 mRNA expression was significantly upregulated in myometrium during inflammation-induced preterm labor compared to preterm no labor. In myometrial cells, IL1B and TNF significantly increased GPR91 mRNA expression. Knockdown of GPR91 by siRNA in myometrial cells significantly suppressed the secretion and/or expression of IL1B- and TNF-induced proinflammatory cytokines (GM-CSF, IL1A, IL1B, and IL6) and chemokines (CXCL8 and CCL2), myometrial contractility (expression of the contraction-associated proteins PTGFR and CX43, secretion of the uterotonic PGF(2 alpha), and in situ collagen gel contraction), and the transcription factor NF-kappa B. Conclusion. Our findings demonstrate that GPR91 is involved in the genesis of proinflammatory and prolabor mediators induced by IL1B or TNF and collectively suggest that GPR91 may contribute to augmentation of the labor processes.