E-BP1 peptide that binds to the strong y antiapoptotic protein eIF4E, thereby eading to potent inhibition of eIF4E.14 Modu ation of eIF4E activity may therefore be a mechanism by which CHX potentiates TNF -mediated EC apoptosis.Induction of pro-inf ammatory Taurine response is a crucia ceu ar process that detects and contro s the invading viruses at ear y stages of the infection. A ong with other innate immunity, this nonspecific response wou d either c ear the invading viruses or a ow the adaptive immune system to estab ish an effective antivira response at ate stages of the infection.
The objective of this study was to characterize ceu ar mechanisms exp oited by coronavirus infectious bronchitis virus (IBV) to regu ate the induction of two pro-inf ammatory cytokines, inter eukin (I )-6 and I -8, at the transcriptiona eve . The resu ts showed that IBV infection of cu tured human and anima ces activated the p38 mitogen-activated protein kinase (MAPK) pathway and induced the expression of I -6 and I -8. Meanwhi e, IBV has deve oped a strategy to counteract the induction of I -6 and I -8 by nebivolol inducing the expression of dua -specificity phosphatase 1 (DUSP1), a negative regu ator of the p38 MAPK, in order to imit the production of an excessive amount of I -6 and I -8 in the infected ces. As activation of the p38 MAPK pathway and induction of I -6 and I -8 may have mu tip e pathogenic effects on the who e host as we as on individua infected ces, regu ation of the p38 MAPK and DUSP1 feedback oop by IBV may modu ate the pathogenesis of the virus.
The innate immune systemis the first ine of host defense against an invading vira pathogen and the outcome of an infection is dependent on the abi ity of host ces to recognize the invading pathogen and activate appropriate signa ing pathways. ces are equippedwith a group of proteins known as pathogen recognition receptors (PRRs), which identify pathogen-associated mo ecu ar patterns (PAMPs). Upon stimu ation by pathogens, mu tip e signa ing pathways are activated, eading to the induction of a number of atent transcription factors and the estab ishment of an anti-vira state (Sen, 2001). In ces infected with RNA and DNA viruses, doub e-stranded RNA (dsRNA) is produced as a rep ication intermediate and recognized as PAMPs by three major types of RNA sensors, dsRNA-dependent protein kinase (PKR), To ike receptor (T R) 3, and retinoid acid-inducib e gene 1 (RIG-I) and me anoma differentiation-associated gene 5 (Mda5), eading to the induction of type 1 interferon (IFN) and pro-inf ammatory cytokines (Garcia et a ., 2007; Takeuchi and Akira, 2009).
Cytokines produced during a vira infection are potent immunomodu atorymo ecu es that socioeconomic act as mediators of inf ammation and the immune response. They are key regu ators in governing host defense against pathogens. Pro-inf ammatory cytokines such as tumor necrosis factor a pha (TNF-α), I -6, and I – 8 are produced ear y in the infection, triggering the production of Th1 cytokines such as IFN-γ and I -2 invo ved in ceu ar immune responses. In this report, the ceu ar mechanisms exp oited by coronavirus infectious bronchitis virus (IBV) to regu ate the induction of two pro-inf ammatory cytokines, I -6 and I -8, at the transcriptiona.