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Interplay between complement factor B and Toll‐like receptors and its role in septic cardiomyopathy
Author(s) -
Zou Lin,
Li Yan,
Feng Yan,
Zhang Ming,
Chen Chan,
Chao Wei
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.652.6
Subject(s) - tlr4 , tlr2 , sepsis , receptor , lipopolysaccharide , complement system , cytokine , western blot , immunology , biology , medicine , antibody , gene , biochemistry
Objective The goal of the current study was to determine whether complement factor B (cfB) would interplay with Toll‐like receptors (TLRs) during sepsis and whether or not such interplay would contribute to septic cardiomyopathy. Methods Cardiomyocytes (CMs) were isolated from wild‐type (WT) mice or mice deficient of TLR2 or TLR4. Polymicrobial sepsis was created by cecum ligation and puncture (CLP). cfB mRNA and protein were determined by qRT‐PCR and Western blot, respectively. Cytokines were determined using a fluorescent multiplex assay. Left ventricular function was assessed in a Langendorff perfusion system. Results Both Pam3cys and lipopolysaccharide (LPS) markedly increased cfB mRNA expression in CMs via TLR2‐ and TLR4‐dependent manner (fold, 217±54 and 578±54, respectively), but not complement 3, 4 or 5. TLR2, TLR3, TLR4 ligands also induced marked cfB protein expression in and release from CMs. In vivo , CLP led to a marked and time‐dependent increase in cfB mRNA and protein expression in septic heart via MyD88‐dependent manner. Importantly, compared with septic WT mice, septic cfB‐KO mice had improved LV function, better survival rate, and decreased cytokine production. Conclusion cfB is up‐regulated in response to TLR activation and polymicrobial sepsis via TLR‐dependent manner. cfB deficiency confers a beneficial effect in cardiac function during sepsis. This research has been supported by NIH R01‐GM080906 and R01‐GM097259.