Leptospira outer membrane protein activates NF-κB and downstream genes expressed in medullary thick ascending limb cells

Chih Wei Yang, Mai Szu Wu, Ming Jeng Pan, Jenn Jye Hong, Chun Chen Yu, Alain Vandewalle, Chiu Ching Huang

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Tubulointerstitial nephritis is the main manifestation of acute renal damage caused by leptospirosis, but the mechanism remains unexplored. Patients infected with Leptospira shermani in Taiwan disclosed tubular dysfunction particularly in the medullary thick ascending limb of loop of Henle (mTAL), and the related renal damage seems to be underestimated. To elucidate the mechanism of tubular damage, outer membrane protein extract from Leptospira was administered to a model of cultured mTAL cells derived from normal mice. The addition of outer membrane protein extract from L. shermani to cultured mTAL cells induced a significant nuclear DNA binding of the NF-κ B transcription factor by electrophoresis mobility shift assay. Forty-eight h after adding the outer membrane protein extract (0.2 μg/ml) to the cultured cells, the expression of inducible nitric oxide mRNA increased by 4.2-fold, monocyte chemoattractant protein-1 by 3-fold, and tumor necrosis factor-α by 2.4-fold when compared with untreated cells examined by reverse transcription competitive-PCR. Supernatant nitrite, monocyte chemoattractant protein-1, and tumor necrosis factor-α protein levels also increased by 1.8-, 7.1-, and 5-fold, respectively. An antiserum raised against L. shermani largely prevented these effects. Outer membrane protein extract from L. bratislava induced fewer effects than L. shermani, and the avirulent nonpathogenic L. biflexa serovar patoc did not induce significant effects in the mTAL cells. In conclusion, L. shermani infection may cause mTAL cell damage and inflammation through the NF-κ B-associated pathway. Findings of this study may be important in understanding the pathogenesis of tubulointerstitial nephritis caused by these organisms.

Original languageEnglish
Pages (from-to)2017-2026
Number of pages10
JournalJournal of the American Society of Nephrology
Volume11
Issue number11
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Loop of Henle
Leptospira
Membrane Proteins
Extremities
Interstitial Nephritis
Chemokine CCL2
Genes
Chemokine CCL7
Tumor Necrosis Factor-alpha
Kidney
Leptospirosis
Electrophoretic Mobility Shift Assay
Nitrites
Taiwan
Reverse Transcription
Electrophoresis
Immune Sera
Cultured Cells
Nitric Oxide
Transcription Factors

ASJC Scopus subject areas

  • Nephrology

Cite this

Leptospira outer membrane protein activates NF-κB and downstream genes expressed in medullary thick ascending limb cells. / Yang, Chih Wei; Wu, Mai Szu; Pan, Ming Jeng; Hong, Jenn Jye; Yu, Chun Chen; Vandewalle, Alain; Huang, Chiu Ching.

In: Journal of the American Society of Nephrology, Vol. 11, No. 11, 2000, p. 2017-2026.

Research output: Contribution to journalArticle

Yang, Chih Wei ; Wu, Mai Szu ; Pan, Ming Jeng ; Hong, Jenn Jye ; Yu, Chun Chen ; Vandewalle, Alain ; Huang, Chiu Ching. / Leptospira outer membrane protein activates NF-κB and downstream genes expressed in medullary thick ascending limb cells. In: Journal of the American Society of Nephrology. 2000 ; Vol. 11, No. 11. pp. 2017-2026.
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