Production of colony-stimulating factors and IL-5 by organs from three types of mice with inflammatory disease due to loss of the suppressor of cytokine signaling-1.
Organs from neonatal mice dying from IFN-gamma-dependent inflammatory disease initiated by loss of the gene encoding the suppressor of cytokine signaling-1 (SOCS-1) had a normal capacity to produce G-CSF in vitro but a reduced capacity to produce GM-CSF, most evident with the lung, and some reduction in the production of M-CSF by muscle tissue. In contrast, organs from mice lacking the genes for both SOCS-1 and IFN-gamma had a normal capacity to produce CSFs. Organs from young adult mice dying with polymyositis and myocarditis that lacked SOCS-1 but were heterozygous for IFN-gamma had a normal capacity to produce GM-CSF and M-CSF, but muscle tissue produced significantly increased amounts of G-CSF and IL-5 with IL-5 production also being elevated for the salivary gland, thymus, and heart. Loss of the IFN-gamma gene alone had no impact on organ production of these cytokines in vitro. In none of the inflammatory disease models was IL-3 production detected. The SOCS-1 protein appears to have no direct influence on the cellular production of these cytokines and the abnormalities observed either depend on the coaction of IFN-gamma, or more likely, are linked with the invasion and destruction of tissue by T lymphocytes, macrophages, eosinophils, and neutrophils. The ability of local organs to produce these proinflammatory cytokines could contribute to the development and progression of these inflammatory lesions.
Metcalf
D
D
Walter and Eliza Hall Institute of Medical Research and the Cooperative Research Centre for Cellular Growth Factors, Royal Melbourne Hospital, Victoria, Australia. metcalf@wehi.edu.au
Alexander
W S
WS
Ryan
P J
PJ
Mifsud
S
S
Di Rago
L
L
D000818:Animals; D001842:Bone and Bones / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics*; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000276:immunology; D009205:Myocarditis / Q000276:immunology; D009206:Myocardium / Q000276:immunology; D009220:Myositis / Q000276:immunology; D009924:Organ Culture Techniques; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013950:Thymus Gland / Q000276:immunology
D002352:Carrier Proteins; D003115:Colony-Stimulating Factors; D015848:Interleukin-5; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor