백서 Mesangial Cell에서 MCP -1 및 CIMC Chemokine의 유전자 발현과 decamethasone 이에 미치는 영향

Macrophage and leukocyte infiltration into the ki- dney is thought to play an important role in the pathogenesis of renal dysfunction in acute and chro- nic glomerulonephritis. Recently a family of chemotactic cytokine(chemo- kine) which recruit and activate macrophage and leukocyte at sites of inflammation, has been iden- tified including MCP-1 as a monocyte chemoattrac- tant protein and CINC as a neutrophil chemoattrac- tant protein in rat. MCP-1 can be generated both by infiltrating ma- crophage as well as by the resident renal cell, especially mesangial cell under the influence of some proinflammatory cytokine. Thus the cross-talk through chemokines between macrophage/neutrophil and mesangial cell can lead to glomerular and inter- stitial injury which ultimately may result in glo- merular sclerosis and interstitial fibrosis. On the other hand, little is known about the gene expres- sion of CINC chemokine in mesangial cell. In this study, we sought to determine whether mesangial cell could be the source of MCP-1 and especially CINC chemokine and whether mesangial expression of these chemokine Mrna could be mo- dulated by dexamethasone. Northern blot assay revealed that interleukin-1B induced MCP-1 and CINC chemokine gene expres- sion in quiescent rat mesangial cell in a dose and time dependent manner. Interleukin-1B induced MCP- 1 and CINC Mrna were peaked after 3 hour and persisted for at least 48 hours respectively. Tumor necrosis factor a, lipopolysaccharide also induced MCP-1 gene expression in a similar fashion. Dexa- methasone suppressed the interleukin-1B induced MCP-1 and CINC chemokine gene expression in a dose dependent manner at 10 -10 'M. Thus mesangial cell would be able to communi- cate directly with macrophage and neutrophil through these chemokines.