Neuroendocrine-induced synthesis of bone marrow-derived cytokines with inflammatory immunomodulating properties

Michael Whetsell, E. Umit Bagriacik, Gattadahalli Seetharamaiah, Bellur S. Prabhakar, John R. Klein

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Although cytokines and other soluble regulators of immunity are known to be involved in hematopoiesis, little is known about the signals that induce the synthesis of those mediators locally. Based on recent studies linking the neuroendocrine hormone thyrotropin [thyroid-stimulating hormone (TSH)] to immune cell function in other tissues, we investigated the capacity of TSH to activate cytokine responses from bone marrow cells. These studies reveal that stimulation of the TSH receptor on bone marrow cells - using highly purified or recombinant TSH or by direct stimulation with anti-TSH receptor antibodies - rapidly induces the synthesis of cytokines from bone marrow cells that are classically used in the regulation of inflammatory responses. Of 13 cytokines screened for activity by ELISA or by RNase protection assays for gene expression, IL-6, IFN-β, TNFα,, TNFβ, TGFβ2, and lymphotoxin-β responses were reproducibly induced by TSH within 2-3 h of stimulation. Intracellularly, TSH stimulation of bone marrow cells caused rapid increases in cAMP levels and induced the phosphorylation of the Jak2 protein kinase, thereby defining a novel G-protein-coupled receptor/cytokine synthesis pathway. These findings demonstrate that TSH can serve as a primary inductive signal of cytokine production by bone marrow cells.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalCellular Immunology
Volume192
Issue number2
DOIs
StatePublished - Mar 15 1999
Externally publishedYes

Fingerprint

Thyrotropin
Bone Marrow
Cytokines
Bone Marrow Cells
Thyrotropin Receptors
Lymphotoxin-alpha
Hematopoiesis
Ribonucleases
G-Protein-Coupled Receptors
Protein Kinases
Immunity
Interleukin-6
Enzyme-Linked Immunosorbent Assay
Phosphorylation
Hormones
Gene Expression
Antibodies

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Neuroendocrine-induced synthesis of bone marrow-derived cytokines with inflammatory immunomodulating properties. / Whetsell, Michael; Bagriacik, E. Umit; Seetharamaiah, Gattadahalli; Prabhakar, Bellur S.; Klein, John R.

In: Cellular Immunology, Vol. 192, No. 2, 15.03.1999, p. 159-166.

Research output: Contribution to journalArticle

Whetsell, Michael ; Bagriacik, E. Umit ; Seetharamaiah, Gattadahalli ; Prabhakar, Bellur S. ; Klein, John R. / Neuroendocrine-induced synthesis of bone marrow-derived cytokines with inflammatory immunomodulating properties. In: Cellular Immunology. 1999 ; Vol. 192, No. 2. pp. 159-166.
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