After the inducing-stimuli and its production, SOCS proteins act as endogenous Fulvestrant negative regulators of inflammatory attenuating cytokine-induced signal

transduction affecting primarily the JAK-STAT pathway, as part of a negative feedback loop to suppress the downstream effects of cytokines. Therefore, in accordance with our findings, SOCS is usually absent or minimally expressed in healthy tissues, and their up-regulation and differential expression in inflamed tissues is an important regulatory mechanism that may influence the outcome of inflammatory reaction.12 and 15 The increased levels of SOCS proteins in the experimental group are consistent with data from literature showing that SOCS expression can be induced by inflammatory cytokines present in diseased periodontal tissues such as IL-6, INF-γ and TNF-α.2, 16 and 17 Furthermore, biopsies of selleckchem inflamed/diseased gingival tissues show higher SOCS1 and -3 mRNA expression when compared with control group without

disease.11 In addition to the host-derived cytokines, the increased microbial burden associated with the transition from periodontal health to disease can also induce expression of SOCS proteins.18 and 19 Since several inflammatory mediators may regulate SOCS expression,20 the nature of inflammatory process in periodontal tissues can influence SOCS production by different cell types. Our results show that the expression of (-)-p-Bromotetramisole Oxalate SOCS protein mirror inflammation

degree/intensity and bone loss during periodontal disease progression. In diseased tissues, already at 7 days, SOCS protein expression had a significant increase, followed by a significant decrease on remaining experimental periods. These results indicate a strong association of SOCS expression and the inflammatory status and density of inflammatory cells, suggesting the kinetic involvement of these cells, or its products/cytokines, and SOCS expression. Studies show that the function of SOCS is to prevent transduction of the cytokine signal by binding to specific receptor sites and ultimately preventing activation of STATs.12 and 21 Through a negative feedback regulatory mechanism, increasing STAT activity leads to increased expression of SOCS in an attempt to decrease the very activation status of the JAK/STAT pathway and, consequently, reduce the consequences of prolonged activation of STAT, such as increased expression of inflammatory cytokines (e.g. IL-1β, IL-6 and TNF-α) associated with periodontal tissue destruction.8 and 22 Interestingly and in accordance with the literature, in the diseased periodontium the SOCS1 and SOCS3 proteins expression levels were correlated with the levels of total and phosphorylated (activated) STAT1 and STAT3, respectively.