SUMF2 interacts with interleukin-13 and inhibits interleukin-13 secretion in bronchial smooth muscle cells.
IL-13 is a central mediator of allergic inflammation and secreted by Th2 and bronchial smooth muscle cells (BSMC). However, little is known about the regulation of IL-13 secretion. To address it, a cDNA library of BSMC was screened for the proteins interacted with IL-13 by yeast two-hybridization. Besides IL-13 receptors, human sulfatase modifying factor 2 (SUMF2) was interacted with IL-13. Furthermore, SUMF2 and IL-13 were co-immunoprecipitated from BSMC, which was independent of IL-13 glycosylation. Interestingly, high levels of SUMF2 were expressed by BSMC, accompanied by significantly higher levels of intracellular IL-13, but lower levels of IL-13 secretion from BSMC. In contrast, little of SUMF2 was detected in lymphocytes, accompanied by lower levels of intracellular IL-13, but significantly higher levels of 12 kDa form of IL-13 secretion. Moreover, knockdown of SUMF2 expression by transfection with SUMF2-specific siRNA did not alter IL-13 mRNA transcription, but significantly reduced intracellular IL-13 levels, associated with increased levels of IL-13 secretion from BSMC. While induction of transient SUMF2 expression in lymphocytes failed to modulate IL-13 mRNA transcription. It significantly increased the contents of 12 kDa form of intracellular IL-13, accompanied by significantly reduced levels of IL-13 in their supernatants. In addition, blockage of N-glycosylation by treatment with tunicamycin eliminated 17 kDa form of intracellular IL-13, but failed to promote IL-13 secretion in BSMC. Collectively, our novel data clearly indicated that SUMF2 interacted with IL-13 and inhibited IL-13 secretion in BSMC and lymphocytes, which was independent of IL-13 glycosylation.
Liang
Hongyan
H
Department of Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Li
Zhengjun
Z
Xue
Li
L
Jiang
Xiaofeng
X
Liu
Fang
F
D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011485:Protein Binding; D013429:Sulfatases / Q000235:genetics / Q000378:metabolism*
D018793:Interleukin-13; C500803:SUMF2 protein, human; D013429:Sulfatases