Dectin-1/Syk signaling is involved in Lactobacillus casei cell wall extract-induced mouse model of Kawasaki disease.
Kawasaki disease (KD) is not only the leading cause of childhood acquired heart diseases, but also causes profound coronary artery sequelae due to chronic vascular inflammation in adulthood. Of unknown underlying mechanism, both innate and adaptive immune responses are involved in the pathogenesis of coronary artery lesions (CALs). We investigated the role of dectin-1/spleen tyrosine kinase (Syk) pathway on macrophage in responsive to Lactobacillus casei cell wall extract (LCWE) in vitro and in vivo. We found that LCWE induced in vitro macrophage activation with increased production of IL-6, TNF-α, and MCP-1, concomitantly with Syk activation, and dectin-1 and TLR2 enhancement. In vivo, LCWE induced infiltration of dectin-1(+) macrophages into CALs and cardiac upregulation of IL-6 and MCP-1 on day 14 post-injection. Most importantly, Syk inhibition alleviated LCWE-induced arteritis in BALB/c mice. Blockade of either dectin-1 or Syk significantly inhibited LCWE-induced IL-6 and MCP-1 production both in vitro and in vivo. This study demonstrates that the macrophage dectin-1/Syk-mediated pathway is involved in LCWE-induced CALs and production of IL-6 and MCP-1. Given the functional equivalence of human dectin-1 to murine, the importance of dectin-1/Syk pathway in the development of murine CALs warrants further investigation on their roles in human KD.
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taiwan.
I-Chun
IC
Lin
Jau-Ling
JL
Suen
Shau-Ku
SK
Huang
Shun-Chen
SC
Huang
Hsin-Chun
HC
Huang
Ho-Chang
HC
Kuo
Chi-Chen
CC
Wei
Feng-Shen
FS
Wang
Hong-Ren
HR
Yu
Kuender D
KD
Yang
D000818:Animals; D002473:Cell Wall / Q000276:immunology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007780:Lacticaseibacillus casei / Q000276:immunology*; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009080:Mucocutaneous Lymph Node Syndrome / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D000099181:Dectin-1
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering; D000072377:Syk Kinase; D051195:Toll-Like Receptor 2; D000099181:Dectin-1; C000606896:SYK protein, human; C000606897:Syk protein, mouse