Activated human valvular interstitial cells sustain interleukin-17 production to recruit neutrophils in infective endocarditis

Chiou Yueh Yeh, Chia Tung Shun, Yu Min Kuo, Chiau Jing Jung, Song Chou Hsieh, Yen Ling Chiu, Jeng Wei Chen, Ron Bin Hsu, Chia Ju Yang, Jean San Chia

研究成果: 雜誌貢獻文章同行評審

8 引文 斯高帕斯(Scopus)


The mechanisms that underlie valvular inflammation in streptococcus-induced infective endocarditis (IE) remain unclear. We previously demonstrated that streptococcal glucosyltransferases (GTFs) can activate human heart valvular interstitial cells (VIC) to secrete interleukin-6 (IL-6), a cytokine involved in T helper 17 (Th17) cell differentiation. Here, we tested the hypothesis that activated VIC can enhance neutrophil infiltration through sustained IL-17 production, leading to valvular damage. To monitor cytokine and chemokine production, leukocyte recruitment, and the induction or expansion of CD4+ CD45RA- CD25- CCR6+ Th17 cells, primary human VIC were cultured in vitro and activated by GTFs. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA), and neutrophils and Th17 cells were detected by immunohistochemistry in infected valves from patients with IE. The expression of IL-21, IL-23, IL-17, and retinoic acid receptor-related orphan receptor C (Rorc) was upregulated in GTF-activated VIC, which may enhance the proliferation of memory Th17 cells in an IL-6-dependent manner. Many chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), were upregulated in GTF-activated VIC, which might recruit neutrophils and CD4+ T cells. Moreover, CXCL1 production in VIC was induced in a dose-dependent manner by IL-17 to enhance neutrophil chemotaxis. CXCL1-expressing VIC and infiltrating neutrophils could be detected in infected valves, and serum concentrations of IL-17, IL-21, and IL-23 were increased in patients with IE compared to healthy donors. Furthermore, elevated serum IL-21 levels have been significantly associated with severe valvular damage, including rupture of chordae tendineae, in IE patients. Our findings suggest that VIC are activated by bacterial modulins to recruit neutrophils and that such activities might be further enhanced by the production of Th17-associated cytokines. Together, these factors can amplify the release of neutrophilic contents in situ, which might lead to severe valvular damage.
頁(從 - 到)2202-2212
期刊Infection and Immunity
出版狀態已發佈 - 2015

ASJC Scopus subject areas

  • 寄生物學
  • 微生物學
  • 免疫學
  • 傳染性疾病


深入研究「Activated human valvular interstitial cells sustain interleukin-17 production to recruit neutrophils in infective endocarditis」主題。共同形成了獨特的指紋。