Intravenous calcitriol administration regulates the renin-angiotensin system and attenuates acute lung injury in obese mice complicated with polymicrobial sepsis
Journal
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Journal Volume
141
Date Issued
2021-09-01
Author(s)
Yeh, Chiu-Li
Su, Li-Han
Yeh, Sung-Ling
Abstract
Calcitriol, an active form of vitamin D, has immunomodulatory and anti-inflammatory properties. Vitamin D levels have inverse correlation with sepsis outcomes and obesity may aggravate the severity of the diseases. This study administered calcitriol to investigate its impact on sepsis-induced acute lung injury (ALI) in obese mice. Mice were fed a high-fat diet to induce obesity and were randomly assigned to control or sepsis groups, which were intravenously administered either saline (SS) or calcitriol (SD). Sepsis was induced by cecal ligation and puncture (CLP). Saline or calcitriol was injected 1 h after CLP via tail vein. Mice were sacrificed at either 12 or 24 h post-CLP and survival rates were observed. The results demonstrated that sepsis caused upregulation of inflammatory mediators and downregulation of renin-angiotensin system (RAS)-associated gene expressions in the lungs of obese mice. Cluster of differentiation 68 (CD68) expression and myeloperoxidase (MPO) activities also increased. Calcitriol treatment lowered expressions of blood and lung inflammatory mediators at 12 and/or 24 h after CLP. The RAS-proinflammatory-associated angiotensin type 1 receptor (AT1R) was lower while anti-inflammatory Mas receptor and AT2R expressions were higher at 12 h after CLP than those in the SS group. In addition, the SD group exhibited lower CD68 expression and MPO activity. Lower lung injury scores and higher survival rates were also noted in the SD group. The findings suggest that calcitriol treatment after sepsis induction upregulated RAS-associated anti-inflammatory pathway and decreased immune cell infiltration, which may have alleviated the severity of ALI of obese mice.
Subjects
Angiotensin receptor; CD68; Mas receptor; Myeloperoxidase; Survival rates
SDGs
Other Subjects
angiotensin 1A receptor; angiotensin 2 receptor; arginase; bupivacaine; calcitriol; cathelicidin; CD68 antigen; epidermal growth factor like module containing mucin like hormone receptor like 1; inducible nitric oxide synthase; interleukin 1beta; interleukin 6; keratinocyte derived chemokine; lipid peroxide; lipopolysaccharide; malonaldehyde; MAS receptor; messenger RNA; monocyte chemotactic protein 1; myeloperoxidase; sodium chloride; thiobarbituric acid reactive substance; tight junction protein; tiletamine plus zolazepam; tumor necrosis factor; unclassified drug; xylazine; angiotensin 1 receptor; autacoid; calcitriol; calcium channel stimulating agent; CD68 antigen, human; cytokine; differentiation antigen; leukocyte antigen; peroxidase; acute lung injury; animal experiment; animal model; animal tissue; antigen expression; Article; cecal ligation and puncture-induced sepsis; cell infiltration; controlled study; disease severity; down regulation; enzyme activity; gene expression; immunocompetent cell; inflammation; lung parenchyma; male; mouse; mRNA expression level; nonhuman; obesity; pain; protein expression; regulatory mechanism; renin angiotensin aldosterone system; sepsis; survival rate; tail vein; upregulation; acute lung injury; animal; C57BL mouse; complication; drug effect; gene expression regulation; genetics; lipid diet; lung; metabolism; microbiology; obesity; renin angiotensin aldosterone system; sepsis; survival analysis; Acute Lung Injury; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Calcitriol; Calcium Channel Agonists; Cytokines; Diet, High-Fat; Gene Expression Regulation; Inflammation Mediators; Lung; Male; Mice; Mice, Inbred C57BL; Obesity; Peroxidase; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Sepsis; Survival Analysis; Up-Regulation
Type
journal article