Differential COX-2 induction by viral and bacterial PAMPs: Consequences for cytokine and interferon responses and implications for anti-viral COX-2 directed therapies

摘要: Cyclooxygenase 2 (COX)-2 is induced by bacterial and viral infections has complex, poorly understood roles in anti-pathogen immunity. Here, we use a knock-in luciferase reporter model to image Cox2 expression across range of tissues mice following treatment with the either prototypical pathogen-associated molecular pattern (PAMP), LPS, which activates Toll-like receptor (TLR)4, or poly(I:C), PAMP, TLR3. LPS all examined. In contrast, poly(I:C) elicited milder response, limited subset tissues. A panel cytokines interferons was measured plasma wild-type, Cox1−/− Cox2−/− treated MALP2 (TLR2/6), Pam3CSK4 (TLR2/1), R-848 (TLR7/8) CpG ODN (TLR9), establish whether/how each COX isoform modulates specific PAMP/TLR responses. Only notable loss condition (inactivity, hunching, piloerection). However, TLR agonists produced cytokine responses, many were modulated fashions Cox1 gene deletion. Notably observed opposing effects deletion on responses consistent differing abilities PAMPs induce expression. IL-1β interferon-γ hypothermia LPS. response exhibited enhanced interferon (IFNα,β,γ,λ) related (IP-10, IL-12). These observations suggest that COX-2 selective inhibitor, given early infection, may enhance and/or prolong endogenous thereby increase anti-viral