Expression and secretion of interleukin-1β, tumour necrosis factor-α and interleukin-10 by hypoxia- and serum-deprivation-stimulated mesenchymal stem cells.
To understand the potential paracrine roles of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10), the expression and secretion of these factors by rat bone marrow-derived mesenchymal cells stimulated by hypoxia (4% oxygen) and serum deprivation (hypoxia/SD) were investigated. We found that hypoxia/SD induced nuclear factor kappa Bp65-dependent IL-1β and TNF-α transcription. Furthermore, hypoxia/SD stimulated the translation of pro-IL-1β and its processing to mature IL-1β, although the translation of TNF-α was unchanged. Unexpectedly, the release of IL-1β and TNF-α from hypoxia/SD-stimulated mesenchymal cells was undetectable unless ATP or lipopolysaccharide was present. This result suggests that IL-1β and TNF-α are not responsible for the paracrine effects of mesenchymal cells under ischaemic conditions. We also found that hypoxia/SD induced the transcription and secretion of IL-10, which were significantly enhanced by lipopolysaccharide and the proteasomal inhibitor MG132. Moreover, both the conditioned medium from hypoxia/SD-stimulated mesenchymal cells (MSC-CM) and IL-10 efficiently inhibited cardiac fibroblast proliferation and collagen expression in vitro, suggesting that mesenchymal cell-secreted IL-10 prevents cardiac fibrosis in a paracrine manner under ischaemic conditions. Taken together, these findings may improve understanding of the cellular and molecular basis of the anti-inflammatory and paracrine effects of mesenchymal cells.
Li
Zongwei
Z
Research Center for Cardiovascular Regenerative Medicine, The Ministry of Health, Cardiovascular Institute & Fu Wai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Wei
Hua
H
Deng
Linzi
L
Cong
Xiangfeng
X
Chen
Xi
X
D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D005355:Fibrosis / Q000517:prevention & control; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D019899:Paracrine Communication; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D053583:Interleukin-1beta; D011498:Protein Precursors; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10