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Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system.

Publication ,  Journal Article
Li, Z; Lin, H; Yang, S; Diehl, AM
Published in: Gastroenterology
October 2002

BACKGROUND & AIMS: ob/ob mice are used to study the mechanisms that regulate the progression from steatosis to nonalcoholic steatohepatitis. The livers of ob/ob mice are depleted of CD4-positive natural killer cells, components of the innate immune system that induce anti-inflammatory cytokines. Although this may explain the sensitivity of fatty livers to lipopolysaccharide, why such hepatic CD4-positive natural killer cell depletion occurs is uncertain. Because leptin regulates macrophages, our hypothesis is that leptin deficiency alters Kupffer cell production of cytokines that inhibit (e.g., interleukin [IL]-12) or enhance (e.g., IL-15) hepatic CD4-positive natural killer cell viability. METHODS: Kupffer cell cytokine production and the hepatic content of CD4-positive natural killer cells were compared in ob/ob and lean mice. ob/ob mice were then treated with IL-15 or leptin to determine whether either factor improved their immunologic abnormalities. RESULTS: Compared with control Kupffer cells, ob/ob Kupffer cells produced less IL-15 basally and more IL-12 after lipopolysaccharide stimulation. Treatment of ob/ob mice with IL-15 for 1 week normalizes their hepatic CD4-positive natural killer cell content. Leptin increases the hepatic expression of IL-15 in ob/ob mice and partially replenishes their hepatic CD4-positive natural killer cells. CONCLUSIONS: Leptin deficiency increases hepatic IL-12 and reduces hepatic IL-15 expression. The abnormal production of these Kupffer cell factors promotes hepatic CD4-positive natural killer cell depletion in ob/ob livers.

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Published In

Gastroenterology

DOI

ISSN

0016-5085

Publication Date

October 2002

Volume

123

Issue

4

Start / End Page

1304 / 1310

Location

United States

Related Subject Headings

  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipopolysaccharides
  • Leptin
  • Kupffer Cells
  • Killer Cells, Natural
  • Interleukin-15
  • Interleukin-12
 

Citation

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Li, Z., Lin, H., Yang, S., & Diehl, A. M. (2002). Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system. Gastroenterology, 123(4), 1304–1310. https://doi.org/10.1053/gast.2002.35997
Li, Zhiping, Huizhi Lin, Shiqi Yang, and Anna Mae Diehl. “Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system.Gastroenterology 123, no. 4 (October 2002): 1304–10. https://doi.org/10.1053/gast.2002.35997.
Li Z, Lin H, Yang S, Diehl AM. Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system. Gastroenterology. 2002 Oct;123(4):1304–10.
Li, Zhiping, et al. “Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system.Gastroenterology, vol. 123, no. 4, Oct. 2002, pp. 1304–10. Pubmed, doi:10.1053/gast.2002.35997.
Li Z, Lin H, Yang S, Diehl AM. Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system. Gastroenterology. 2002 Oct;123(4):1304–1310.
Journal cover image

Published In

Gastroenterology

DOI

ISSN

0016-5085

Publication Date

October 2002

Volume

123

Issue

4

Start / End Page

1304 / 1310

Location

United States

Related Subject Headings

  • Mice, Mutant Strains
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipopolysaccharides
  • Leptin
  • Kupffer Cells
  • Killer Cells, Natural
  • Interleukin-15
  • Interleukin-12