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IL-4 and TNF-alpha-mediated proliferation of the human megakaryocytic line M-O7E is regulated by induced autocrine production of GM-CSF.
Cytokine. 1996 Dec; 8(12):900-9.C

Abstract

In this study, the authors examined the effects of recombinant human interleukin 4 (rhIL-4) and recombinant human tumour necrosis factor alpha (rhTNF-alpha) alone or in combination on proliferation of the human cytokine dependent myeloid cell line, M-O7e. While rhIL-4 or rhTNF-alpha alone induced only a weak proliferative response, a synergistic proliferative signal was clearly evident on stimulation of cells with a combination of both cytokines. The stimulatory effect of rhTNF-alpha is mediated predominantly by the 55-kDa TNF receptor because the agonistic monoclonal antibody htr-9 and the Trp32 Thr86 TNF-alpha mutant protein specific for this receptor type produced similar results to rhTNF-alpha. In contrast, the Asn143 Arg145 TNF-alpha mutant protein specific for the 75-kDa TNF receptor produced only minimal proliferation of M-O7e cells. Using RT-PCR, we found that rhTNF-alpha rapidly and strongly induced granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA production, while rhIL-4 was a slow and less efficient inducer of GM-CSF mRNA. However, there was little evidence of the TNF-alpha/IL-4 combination acting synergistically on GM-CSF mRNA production as the levels of GM-CSF mRNA increased only marginally compared with IL-4 or TNF-alpha alone. Thus, the observed synergistic effect of TNF-alpha/IL-4 costimulation of M-O7e cells seems to be mediated via induction of GM-CSF secretion rather than an enhanced production of GM-CSF mRNA. Higher levels of GM-CSF were detectable in supernatants of cells treated with both rhIL-4 and rhTNF-alpha than in cells stimulated with either cytokine alone. Furthermore, addition of a neutralising antibody against GM-CSF abrogated the observed synergistic effect of rhIL-4 and rhTNF-alpha treatment, indicating that the rhIL-4/TNF-alpha combination acts to significantly increase GM-CSF release which then acts in an autocrine manner to enhance the proliferation of M-O7e cells.

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Authors+Show Affiliations

Wadhwa M
Division of Immunobiology, National Institute for Biological Standards and Control, Herts, UK.
Dilger P
No affiliation info available
Meager A
No affiliation info available
Walker B
No affiliation info available
Gaines-Das R
No affiliation info available
Thorpe R
No affiliation info available

MeSH

Antibodies, MonoclonalAntigens, CDCell DivisionCell LineCulture MediaGranulocyte-Macrophage Colony-Stimulating FactorHumansInterleukin-4MegakaryocytesRNA, MessengerReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIRecombinant Fusion ProteinsTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9050748

Citation

Wadhwa, M, et al. "IL-4 and TNF-alpha-mediated Proliferation of the Human Megakaryocytic Line M-O7E Is Regulated By Induced Autocrine Production of GM-CSF." Cytokine, vol. 8, no. 12, 1996, pp. 900-9.
Wadhwa M, Dilger P, Meager A, et al. IL-4 and TNF-alpha-mediated proliferation of the human megakaryocytic line M-O7E is regulated by induced autocrine production of GM-CSF. Cytokine. 1996;8(12):900-9.
Wadhwa, M., Dilger, P., Meager, A., Walker, B., Gaines-Das, R., & Thorpe, R. (1996). IL-4 and TNF-alpha-mediated proliferation of the human megakaryocytic line M-O7E is regulated by induced autocrine production of GM-CSF. Cytokine, 8(12), 900-9.
Wadhwa M, et al. IL-4 and TNF-alpha-mediated Proliferation of the Human Megakaryocytic Line M-O7E Is Regulated By Induced Autocrine Production of GM-CSF. Cytokine. 1996;8(12):900-9. PubMed PMID: 9050748.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-4 and TNF-alpha-mediated proliferation of the human megakaryocytic line M-O7E is regulated by induced autocrine production of GM-CSF. AU - Wadhwa,M, AU - Dilger,P, AU - Meager,A, AU - Walker,B, AU - Gaines-Das,R, AU - Thorpe,R, PY - 1996/12/1/pubmed PY - 1996/12/1/medline PY - 1996/12/1/entrez SP - 900 EP - 9 JF - Cytokine JO - Cytokine VL - 8 IS - 12 N2 - In this study, the authors examined the effects of recombinant human interleukin 4 (rhIL-4) and recombinant human tumour necrosis factor alpha (rhTNF-alpha) alone or in combination on proliferation of the human cytokine dependent myeloid cell line, M-O7e. While rhIL-4 or rhTNF-alpha alone induced only a weak proliferative response, a synergistic proliferative signal was clearly evident on stimulation of cells with a combination of both cytokines. The stimulatory effect of rhTNF-alpha is mediated predominantly by the 55-kDa TNF receptor because the agonistic monoclonal antibody htr-9 and the Trp32 Thr86 TNF-alpha mutant protein specific for this receptor type produced similar results to rhTNF-alpha. In contrast, the Asn143 Arg145 TNF-alpha mutant protein specific for the 75-kDa TNF receptor produced only minimal proliferation of M-O7e cells. Using RT-PCR, we found that rhTNF-alpha rapidly and strongly induced granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA production, while rhIL-4 was a slow and less efficient inducer of GM-CSF mRNA. However, there was little evidence of the TNF-alpha/IL-4 combination acting synergistically on GM-CSF mRNA production as the levels of GM-CSF mRNA increased only marginally compared with IL-4 or TNF-alpha alone. Thus, the observed synergistic effect of TNF-alpha/IL-4 costimulation of M-O7e cells seems to be mediated via induction of GM-CSF secretion rather than an enhanced production of GM-CSF mRNA. Higher levels of GM-CSF were detectable in supernatants of cells treated with both rhIL-4 and rhTNF-alpha than in cells stimulated with either cytokine alone. Furthermore, addition of a neutralising antibody against GM-CSF abrogated the observed synergistic effect of rhIL-4 and rhTNF-alpha treatment, indicating that the rhIL-4/TNF-alpha combination acts to significantly increase GM-CSF release which then acts in an autocrine manner to enhance the proliferation of M-O7e cells. SN - 1043-4666 UR - https://www.unboundmedicine.com/medline/citation/9050748/IL_4_and_TNF_alpha_mediated_proliferation_of_the_human_megakaryocytic_line_M_O7E_is_regulated_by_induced_autocrine_production_of_GM_CSF_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-4666(96)90121-0 DB - PRIME DP - Unbound Medicine ER -

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