We studied the changes in thiol status in mouse retina lacking aA-or aB crystallin

c inflammatory and infectious disease. Thus, much research effort has been focused on understanding the regulation of innate immune responses, yet the underlying mechanisms remain imprecisely characterized. Toll-like receptors are the best characterized PRRs and play 1820332 an important role in the innate immune system. TLRs are transmembrane proteins composed of N-terminal leucine-rich repeats, a transmembrane region, and a cytoplasmic Toll/IL-1R homology domain at the C-terminus. Among TLRs, TLR4 plays a central role in the recognition of both Gram-negative and Gram-positive bacteria. TLR4 is the only TLR which can recruit four different adaptor proteins myeloid differentiation primary response protein 88, Toll/IL-1R domain containing adaptor protein, TIR domain containing adaptor inducing interferon b, and TRIF related adaptor molecule to turn on MyD88- or TRIF-dependent pathways. The MyD88-dependent pathway requires the recruitment of MyD88 and TIRAP, which associate with IL-1R-associated kinase and TNF receptor-associated factor 6. These in turn activate mitogen-activated protein kinases, such as p38, extracellular signal-regulated kinases, Jun N-terminal kinases, and IkB kinase, leading to phosphorylation of the transcription factors, such as nuclear factor kappa B and cAMP response element-binding protein, and then 1 Tnfaip3 is Regulated by NF-kB and p38 via C/EBPb induction of genes encoding cytokines and anti-apoptotic proteins. In contrast, the TRIF-dependent pathway requires the recruitment of TRIF and TRAM, which bind to TNF receptorassociated factor 3, leading to activation of interferon regulatory factor 3 and the expression of type I interferons and IFN-responsive genes. Salianic acid A Recent studies also indicated that the TRIF-dependent pathway mediates late-phase activation of IKK/NF-kB 22988107 and MAPKs, probably through the recruitment of TRAF6 and transforming growth factor b activated kinase 1. More than 1,000 mammalian genes are induced in immune cells after stimulation with LPS, a TLR4 ligand. It is becoming increasingly evident that the expression of LPS-induced genes is regulated in a temporal order, and a highly integrated mechanism must ensure that the expression of these genes is `programmed’ after TLR4 activation. Transcriptional control has been shown to play a crucial role in determining the kinetics of TLR4-mediated gene expression. However, NF-kB, a core transcription factor of the innate immune response, is not the only determinant of gene expression upon TLR4 engagement. Previous reports have demonstrated that, in addition to NF-kB, the expression of some LPS-induced genes in macrophages requires a second transcription factor whose activity depends on p38. Several transcription factors, including CREB, ATF1, and ATF2, have been reported to be modulated by p38 kinase in TLR4-mediated immunity. Yet, these known p38-dependent transcription factors are not able to explain all LPS-induced genes, suggesting that a yet-to-be-identified transcription factor is involved. Therefore, with the goal of better understanding the molecular processes underlying the temporal order of gene expression after TLR4 activation, the purpose of this study was to identify novel p38-dependent transcription factors that cooperate with NF-kB upon LPS stimulation. We used microarray analysis in combination with in silico analysis to identify coincident NF-kB- and p38regulated genes. Among these genes, we demonstrated that Tnfaip3 is regulated by both NF-kB and