Effects of Complement 3 deficiency on its receptor downstream signaling pathway-mediated inflammatory response in knockout mice

Abstract

The current study measured alterations in the inducible nitric oxide synthase (iNOS)‑mediated cyclooxygenase‑2 (COX‑2) induction pathway, inflammasome pathway, NF-kB activation, and inflammatory cytokine expressions in the transverse colon of C3 knockout (KO) mice, to determine whether complement component 3 (C3) deficiency affects its receptor downstream-mediated inflammatory response. Compared to wild type (WT) mice, the expression level of C3 protein was successfully suppressed in the transverse colon of C3 KO mice. Significant enhancement was observed in expression levels of important members of the iNOS‑mediated COX‑2 induction pathway, and in the phosphorylation of mitogen‑activated protein (MAP) kinase members. Also, a similar pattern of increase was observed in the expression levels of inflammasome proteins in C3 KO mice. Moreover, compared to WT mice, C3 KO mice showed remarkably enhanced phosphorylation of NF-kB and IkB-a, which was reflected in entirety as increased expressions of TNF-a, IL-6 and IL-1a. Taken together, results of the current study indicate that C3 deficiency induces activation of the iNOS‑mediated COX‑2 induction pathway, ASC-inflammasome pathway, and NF-kB signaling pathway, resulting in the enhancement of inflammatory cytokine expressions in the transverse colon of C3 KO mice.