1α,25-Dihydroxyvitamin D3 inhibits neutrophil recruitment in hamster model of acute lung injury
Highlights
▸ 1α,25(OH)2D3 inhibits neutrophil recruitment in a model of acute lung injury. ▸ 1α,25(OH)2D3 inhibits neutrophil recruitment stronger than that of dexamethasome. ▸ Neutrophil recruitment was inhibited without increasing plasma Ca concentration. ▸ 1α,25(OH)2D3 dose not affect monocyte recruitment.
Introduction
The hormonally active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), has traditionally been associated with calcium and phosphorus homeostasis and maintenance of skeletal architecture in both young and adult mammals. Vitamin D achieves this prominent physiological role by promoting absorption of dietary calcium and phosphorus from the small intestine and by influencing the number and/or activity of osteoclasts and osteoblasts [1], [2]. Recently, the 1α,25(OH)2D3-vitamin D receptor system was found to mediate immunomodulation to control cytokines such as interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-8, and tumor necrosis factor-alpha [3], [4]. IL-8 is regarded as one of the most important endogenous chemotactic factors for neutrophils, and its infiltration has been observed in conditions such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD) and has been considered associated with lung disorders [5]. However, whether or not 1α,25(OH)2D3 can inhibit neutrophil recruitment in ALI remains unclear. Here we report the inhibition of neutrophil recruitment in hamster ALI by 1α,25(OH)2D3.
Section snippets
Reagents
The reagents used in this study and their sources were as follows: Lipopolysaccharide (LPS; Escherichia coli, 0111:B4) obtained from Difco Laboratories (Detroit, MI). Dexamethasone-21-acetate obtained was purchased from Sigma–Aldrich Co., (St. Louis, MO). Sodium carboxymethylcellulose was obtained from Nacalai Tesque, Inc. (Kyoto, Japan). 1α,25(OH)2D3 was synthesized at the Teijin Institute for Bio-Medical Research. The compound was dissolved in 100% ethanol to determine concentration according
Time-course of LPS-induced acute lung inflammation in hamsters
Inhalation of LPS resulted in acute lung inflammation. The time-course of the number of cells in the BALFs is shown in Fig. 1A. From the differential cell count analysis, monocytes were observed; however, most of the cells in the BALFs were neutrophils. The number of neutrophils increased markedly and peaked at 24 h after LPS inhalation (1.8 × 103 cells/ml at t = 0 and 4.9 × 106 cells/ml at t = 24 h) and then decreased. On the other hand, the number of monocytes showed only a small increase (1.4 × 105
Discussion
Several studies have indicated that 1α,25(OH)2D3 suppresses IL-8 production in several kinds of cells such as normal human dermal fibroblast [9], human whole blood cells [10], primary normal human keratinocytes [11], human primary proximal tubular epithelial cells [12], human fibroblasts derived from nasal polyposis [13], and prostatic hyperplasia stromal cell [14]. Harant et al. reported that 1α,25(OH)2D3 suppresses IL-8 production in human melanoma cell line A3 and MRC-5 fibroblasts through
Acknowledgements
We wish to thank Dr. Seiichi Ishizuka of the University of Pittsburgh, School of Medicine, for reviewing the manuscript. We also wish to thank Ms. Makiko Hasebe for her technical assistance.
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Present address: Home Healthcare Scientific Promotion Department, Teijin Pharma Limited, Tokyo 100-8585, Japan.