Cytokine Regulation of Parathyroid Hormone-Related Protein Messenger Ribonucleic Acid Levels in Mouse Spleen: Paradoxical Effects of Interferon-γ and Interleukin-4

Janet L Funk, Judy K. Shigenaga, Arthur H. Moser, Eveline J T Krul, Gordon J. Strewler, Kenneth R. Feingold, Carl Grunfeld

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Under normal physiological conditions, PTH-related protein (PTHrP) is produced in a wide variety of tissues and is thought to act locally in an autocrine or paracrine fashion more analogous to cytokines than to classic hormones such as PTH. In addition, we have recently shown that, like cytokines, PTHrP is induced in the spleen during the response to sublethal doses of endotoxin [lipopolysaccharide (LPS)] an effect that is mediated by tumor necrosis factor (TNF). As complex cytokine cascades are induced in response to infectious or inflammatory stimuli, the effects of other prototypical inflammatory [interferon-γ (IFNγ)] or antiinflammatory [interleukin-4 (IL-4)] cytokines on PTHrP gene expression were studied. Paradoxically, IFN-γ (50 μg), a cytokine that usually synergizes with TNF, inhibited LPS induction of splenic PTHrP messenger RNA (mRNA) levels in LPS-sensitive C3H/ OuJ (OuJ) and LPS-resistant C3H/HeJ (HeJ) mice. The stimulation of splenic PTHrP mRNA levels caused by the administration of TNFα or interleukin-1β was similarly inhibited by IFNγ, a type II interferon. In contrast, IFNα (50 μ), a type I interferon, stimulated splenic levels of PTHrP mRNA. IL-4, a prototypical antiinflammatory cytokine, also had a paradoxical effect on LPS induction of splenic PTHrP mRNA levels. Instead of inhibiting LPS induction of splenic PTHrP mRNA levels in OuJ or HeJ mice, IL-4 (200 ng) actually stimulated PTHrP mRNA levels. These complex cytokine interactions suggest that the expression of PTHrP in response to infectious or inflammatory stimuli depends on the counterbalancing effects of the specific cytokine networks induced by each stimulus.

Original languageEnglish (US)
Pages (from-to)351-358
Number of pages8
JournalEndocrinology
Volume135
Issue number1
StatePublished - Jul 1994
Externally publishedYes

Fingerprint

Parathyroid Hormone-Related Protein
Interleukin-4
Interferons
Spleen
RNA
Cytokines
Lipopolysaccharides
Proteins
Messenger RNA
Tumor Necrosis Factor-alpha
Interferon-gamma
Anti-Inflammatory Agents
Interferon Type I
Interleukin-1
Endotoxins
Hormones
Gene Expression

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Funk, J. L., Shigenaga, J. K., Moser, A. H., Krul, E. J. T., Strewler, G. J., Feingold, K. R., & Grunfeld, C. (1994). Cytokine Regulation of Parathyroid Hormone-Related Protein Messenger Ribonucleic Acid Levels in Mouse Spleen: Paradoxical Effects of Interferon-γ and Interleukin-4. Endocrinology, 135(1), 351-358.

Cytokine Regulation of Parathyroid Hormone-Related Protein Messenger Ribonucleic Acid Levels in Mouse Spleen : Paradoxical Effects of Interferon-γ and Interleukin-4. / Funk, Janet L; Shigenaga, Judy K.; Moser, Arthur H.; Krul, Eveline J T; Strewler, Gordon J.; Feingold, Kenneth R.; Grunfeld, Carl.

In: Endocrinology, Vol. 135, No. 1, 07.1994, p. 351-358.

Research output: Contribution to journalArticle

Funk, Janet L ; Shigenaga, Judy K. ; Moser, Arthur H. ; Krul, Eveline J T ; Strewler, Gordon J. ; Feingold, Kenneth R. ; Grunfeld, Carl. / Cytokine Regulation of Parathyroid Hormone-Related Protein Messenger Ribonucleic Acid Levels in Mouse Spleen : Paradoxical Effects of Interferon-γ and Interleukin-4. In: Endocrinology. 1994 ; Vol. 135, No. 1. pp. 351-358.
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