Co-regulated expression of glomerular 12/15-lipoxygenase and interleukin-4 mRNAs in rat nephrotoxic nephritis

Tetsuo Katoh, Fadi G. Lakkis, Naomasa Makita, Kamal F. Badr

Research output: Contribution to journalArticle

Abstract

Arachidonate 12- and 15-lipoxygenase (LO) products are generated in experimental glomerulonephritis. 15-S-HETE (a 15-LO product) and lipoxins (interaction products between 5-LO and either 12-LO or 15-LO) counteract the proinflammatory actions of leukotrienes. IL-4 has been shown to up-regulate 15-LO gene expression in human leukocytes. Based on homology with human 15-LO, we cloned a 0.76 kbp fragment of a rat LO cDNA from leukocytes stimulated by interleukin-4 (IL-4). The deduced amino acid sequence shows 71.0% and 60.1% homology to human 15-LO and 12-LO, respectively, and 100% homology to a recently cloned "leukocyte type" rat 12-lipoxygenase enzyme, which possesses significant 15-lipoxygenase activity (heretofore referred to as "12/15-LO"). A deletion mutant was utilized to generate internal standard cRNA in quantitative PCR assays. Glomerular 12/15-LO mRNA increased significantly over controls 24 and 48 hours after NTS injection, then decreased at 72 hours. RNA from NTS glomeruli contained higher levels of 12/15-LO mRNA than that from unstimulated peripheral leukocytes, suggesting that 12/15-LO transcription is up-regulated locally in native and/or infiltrating glomerular cells. Glomerular IL-4 mRNA increased markedly 16 hours post-NTS, and was then reduced, suggesting a potential role for T cell-derived IL-4 in directing the expression of 12/15-LO during glomerulonephritis. This represents the first demonstration of tandem regulated in vivo gene expression for a lymphokine (IL-4) and a lipoxygenase, both of which promote counter-inflammatory influences in immune complex-mediated injury.

Original languageEnglish (US)
Pages (from-to)341-349
Number of pages9
JournalKidney International
Volume46
Issue number2
StatePublished - Aug 1994
Externally publishedYes

Fingerprint

Arachidonate 15-Lipoxygenase
Nephritis
Interleukin-4
Arachidonate 12-Lipoxygenase
Messenger RNA
Leukocytes
Lipoxygenase
Glomerulonephritis
Lipoxins
Gene Expression
Arachidonate 5-Lipoxygenase
Complementary RNA
Leukotrienes
Lymphokines
12-15-lipoxygenase
Antigen-Antibody Complex
Amino Acid Sequence
Up-Regulation
Complementary DNA
RNA

ASJC Scopus subject areas

  • Nephrology

Cite this

Co-regulated expression of glomerular 12/15-lipoxygenase and interleukin-4 mRNAs in rat nephrotoxic nephritis. / Katoh, Tetsuo; Lakkis, Fadi G.; Makita, Naomasa; Badr, Kamal F.

In: Kidney International, Vol. 46, No. 2, 08.1994, p. 341-349.

Research output: Contribution to journalArticle

Katoh, Tetsuo ; Lakkis, Fadi G. ; Makita, Naomasa ; Badr, Kamal F. / Co-regulated expression of glomerular 12/15-lipoxygenase and interleukin-4 mRNAs in rat nephrotoxic nephritis. In: Kidney International. 1994 ; Vol. 46, No. 2. pp. 341-349.
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