Surfactant protein D inhibits lipopolysaccharide-induced monocyte chemoattractant protein-1 expression in human renal tubular epithelial cells: implication for tubulointerstitial fibrosis

Clin Exp Immunol. 2012 Mar;167(3):514-22. doi: 10.1111/j.1365-2249.2011.04521.x.

Abstract

Surfactant protein D (SP-D), a member of the C-type lectin (collectin) protein family, plays a critical role in innate host defence against various microbial pathogens and in the modulation of inflammatory responses in the lung. However, little is known about its expression and biological function in the kidney. In this work, we studied SP-D expression in human kidney and cultured human renal proximal tubular epithelial cells (HK-2), and examined the effect of SP-D on proinflammatory cytokine production after lipopolysaccharide (LPS) stimulus. We observed the expression of both SP-D mRNA and protein in human kidney and in-vitro HK-2 cells by immunohistochemistry, Western blot analysis, reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. To explore the potential role of SP-D in the pathogenesis of tubulointerstitial fibrosis in kidney infection, we examined the production of monocyte chemoattractant protein-1 (MCP-1) in HK-2 cells after LPS treatment. Results showed that the level of MCP-1 in the conditioned medium increased significantly when HK-2 cells were cultured with LPS (>0·1 µg/ml) for 8 h. Of interest, LPS treatment inhibited SP-D expression in HK-2 cells. Furthermore, over-expression of SP-D reduced significantly the LPS-induced expression of MCP-1 in transfected cells. These findings suggest that SP-D in the kidney functions as an anti-inflammatory factor in renal tubular epithelial cells and may modulate tubulointerstitial fibrosis in kidney.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / genetics
  • Culture Media, Conditioned
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Fibrosis
  • Gene Expression / drug effects
  • Humans
  • Kidney Diseases / etiology
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects
  • Kidney Tubules / immunology*
  • Kidney Tubules / metabolism*
  • Lipopolysaccharides / pharmacology
  • Pulmonary Surfactant-Associated Protein D / genetics
  • Pulmonary Surfactant-Associated Protein D / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Culture Media, Conditioned
  • Lipopolysaccharides
  • Pulmonary Surfactant-Associated Protein D
  • RNA, Messenger
  • Recombinant Proteins