In vitro effects of Habu snake venom on cultured mesangial cells.
BACKGROUND
Habu snake venom (HSV)-induced glomerulonephritis is a unique model showing a progressive course of mesangial proliferation. To elucidate the in vitro effects of HSV, we examined whether HSV itself could have direct effects on the cultured mesangial cells, such as cell proliferation and activation of chemokine gene expression.


METHODS
The incorporation of 5-[(125)I]iodo-2'-deoxyuridine was measured with a gamma-counter, and gene expressions of growth factors, chemokines and cytokines were evaluated by a real time quantitative PCR.


RESULTS
We demonstrated that excessive or continuous HSV stimulation decreased a mesangial cell viability. However, adequate and temporary HSV stimulation induced proliferation of mesangial cells in vitro along with a significant elevation of monocyte chemoattractant protein-1 (MCP-1) mRNA levels. In addition to these in vitro results, we showed that MCP-1 mRNA levels increased in renal cortices of glomerulonephritis induced by HSV. Immunohistochemistry also showed a positive staining for MCP-1 in the marginal area of glomerulus with mesangiolysis.


CONCLUSIONS
These data suggest that HSV itself may elicit direct biological effects on mesangial cells which may participate in pathophysiology of glomerulonephritis induced by HSV.
Kubo
Atsushi
A
Department of Public Health, Nara Medical University, Kashihara, Nara, Japan.
Iwano
Masayuki
M
Kobayashi
Yoshiyuki
Y
Kyoda
Yusuke
Y
Isumi
Yoshitaka
Y
Maruyama
Naoki
N
Samejima
Kenichi
K
Dohi
Yoshiko
Y
Minamino
Naoto
N
Yonemasu
Kunio
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics; D003435:Crotalid Venoms / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D005920:Glomerular Mesangium / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D006133:Growth Substances / Q000235:genetics; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017841:Trimeresurus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018932:Chemokine CCL2; D003435:Crotalid Venoms; D006133:Growth Substances; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004247:DNA