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Enhanced LL ‐37 expression following vitamin D supplementation in patients with cirrhosis and spontaneous bacterial peritonitis
Author(s) -
Zhang Chong,
Zhao Lianrong,
Ding Yang,
Sheng Qiuju,
Bai Han,
An Ziying,
Xia Tingting,
Wang Jingyan,
Dou Xiaoguang
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12888
Subject(s) - calcitriol receptor , spontaneous bacterial peritonitis , cirrhosis , vitamin d and neurology , pathogenesis , medicine , incubation , endocrinology , lipopolysaccharide , vitamin , vitamin d deficiency , macrophage , chemistry , in vitro , biochemistry
Background & Aims The morbidity and mortality of spontaneous bacterial peritonitis ( SBP ) are high among patients with cirrhosis; however, the mechanisms of SBP pathogenesis are poorly understood. This study aimed to determine the role of the vitamin D‐ LL ‐37 pathway in the pathogenesis and treatment in patients with cirrhosis and SBP . Methods Serum 25‐hydroxyvitamin D concentrations of 119 patients with chronic liver diseases were tested. Vitamin D receptor ( VDR ) and LL ‐37 in peritoneal leucocytes of cirrhotic and ascitic patients with SBP were detected and compared with those without SBP . Then the peritoneal macrophages of non‐infected patients were cultured and activated by lipopolysaccharide ( LPS ) to analyse the changes of VDR and LL ‐37 expressions after incubation with vitamin D. Results Vitamin D deficiency or insufficiency was found in all of patients with cirrhosis. LPS inhibited VDR and LL ‐37 expression in peritoneal macrophages [1.3‐fold decrease ( P = 0.003) and 20‐fold decrease ( P = 0.010) respectively]. However, vitamin D could reverse the inhibition of both VDR and LL ‐37 [1.5‐fold increase ( P = 0.001) and 2000‐fold increase ( P < 0.001) respectively]. The effect of the incubation time following vitamin D supplementation was significant for LL ‐37 expression, with a peak expression found at 36 h ( P < 0.001). Conclusions When vitamin D levels were low, bacteria inhibited VDR and LL ‐37 responses in peritoneal macrophages as a mechanism to evade antibacterial defence. Vitamin D supplementation could up‐regulate peritoneal macrophage VDR and LL ‐37 expressions, which resulted in an enhanced immunological defence against SBP in patients with cirrhosis and ascites.