Interleukin-4 Down-regulates Both Forms of Tumor Necrosis Factor Receptor and Receptor-mediated Apoptosis, NF-κB, AP-1, and c-Jun N-Terminal Kinase

Manna, Sunil K.; Aggarwal, Bharat B.

doi:10.1074/jbc.273.50.33333

Cited by 65 publications

(44 citation statements)

References 40 publications

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“…The differential capacity of IL-4 to block activation of signals by the closely related molecules, TNF and RANKL, provides evidence for receptor-mediated signaling specificity. Finally, contrary to the report that IL-4 down-regulates both the p55 and p75 TNF receptors in transformed myeloid cells (48), thereby totally abrogating TNF-induced signaling, we find that in primary BMMs the T cell-derived cytokine inhibits some, but not all, components of TNF-induced signaling.…”

Section: Interleukin-4 and Osteoclastogenesiscontrasting

confidence: 55%

Interleukin-4 Reversibly Inhibits Osteoclastogenesis via Inhibition of NF-κB and Mitogen-activated Protein Kinase Signaling

Shi

Wang

Teitelbaum

et al. 2002

Journal of Biological Chemistry

192

141

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To define the molecular mechanism(s) by which interleukin (IL)-4 reversibly inhibits formation of osteoclasts (OCs) from bone marrow macrophages (BMMs), we examined the capacity of this T cell-derived cytokine to impact signals known to modulate osteoclastogenesis, which include those initiated by macrophage colonystimulating factor (M-CSF), receptor for activation of NF-B ligand (RANKL), tumor necrosis factor (TNF), and IL-1. We find that although pretreatment of BMMs with IL-4 does not alter M-CSF signaling, it reversibly blocks RANKL-dependent activation of the NF-B, JNK, p38, and ERK signals. IL-4 also selectively inhibits TNF signaling, while enhancing that of IL-1. Contrary to previous reports, we find that MEK inhibitors dose-dependently inhibit OC differentiation. To identify more proximal signals mediating inhibition of OC formation by IL-4, we used mice lacking STAT6 or SHIP1, two adapter proteins that bind the IL-4 receptor. IL-4 fails to inhibit RANKL/M-CSF-induced osteoclastogenesis by BMMs derived from STAT6-, but not SHIP1-, knockout mice. Consistent with this observation, the inhibitory effects of IL-4 on RANKL-induced NF-B and mitogen-activated protein kinase activation are STAT6-dependent. We conclude that IL-4 reversibly arrests osteoclastogenesis in a STAT6-dependent manner by 1) preventing IB phosphorylation and thus NF-B activation, and 2) blockade of the JNK, p38, and ERK mitogen-activated protein kinase pathways.

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Section: Interleukin-4 and Osteoclastogenesiscontrasting

confidence: 55%

Interleukin-4 Reversibly Inhibits Osteoclastogenesis via Inhibition of NF-κB and Mitogen-activated Protein Kinase Signaling

Shi

Wang

Teitelbaum

et al. 2002

Journal of Biological Chemistry

192

141

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“…41 IL-4 also downregulates the expression of 2 distinct receptors for TNF-␣, p60, and p80 and induces shedding of these receptors, resulting in blockage of the cellular signaling elicited by TNF-␣. 42 Moreover, several investigators have shown that IL-4 antagonizes IFN-␥-induced responses in human myeloid progenitor and mature cells. [43][44][45] Therefore, we have no plausible explanation for the mechanism of action of IL-4 on CD15 ϩ CD14 Ϫ neutrophils during their lineage switch to macrophages.…”

Section: Discussionmentioning

confidence: 99%

Reprogramming of human postmitotic neutrophils into macrophages by growth factors

Araki

Katayama

Yamashita

et al. 2004

Blood

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It is generally recognized that postmitotic neutrophils give rise to polymorphonuclear neutrophils alone. We obtained evidence for a lineage switch of human postmitotic neutrophils into macrophages in culture. When the CD15 ؉ CD14 ؊ cell population, which predominantly consists of band neutrophils, was cultured with granulocyte macrophage-colonystimulating factor, tumor necrosis factor-␣, interferon-␥, and interleukin-4, and subsequently with macrophage colonystimulating factor alone, the resultant cells had morphologic, cytochemical, and phenotypic features of macrophages. In contrast to the starting population, they were negative for myeloperoxidase, specific esterase, and lactoferrin, and they upregulated nonspecific esterase activity and the expression of macrophage colony-stimulating factor receptor, mannose receptor, and HLA-DR. CD15 ؉ CD14 ؊ cells proceeded to macrophages through the CD15 ؊ CD14 ؊ cell population. Microarray analysis of gene expression also disclosed the lineage conversion from neutrophils to macrophages. Macrophages derived from CD15 ؉ CD14 ؊ neutrophils had phagocytic function. Data obtained using 3 different techniques, including Ki-67 staining, bromodeoxyuridine incorporation, and cytoplasmic dye labeling, together with the yield of cells, indicated that the generation of macrophages from CD15 ؉ CD14 ؊ neutrophils did not result from a contamination of progenitors for macrophages. Our data show that in response to cytokines, postmitotic neutrophils can become macrophages. This may represent another differentiation pathway toward macrophages in human postnatal

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“…The specific activities of radiolabeled ligands were 0.5 Â 10 7 to 1 Â 10 7 cpm/lg protein. Cell surface receptors for different ligands were detected following the method as described previously [29].…”

Section: Neutrophil and Macrophage Differentiation And Isolationmentioning

confidence: 99%

“…To estimate the number of CXCR expressed on a-MSHtreated neutrophils, Scatchard analysis was performed [28,29]. Cells, either untreated or treated with a-MSH Fig.…”

Section: A-msh Inhibits Il-8 Bindingmentioning

confidence: 99%

α‐melanocyte‐stimulating hormone down‐regulates CXC receptors through activation of neutrophil elastase

2006

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Considering the role of interleukin-8 (IL-8) in a large number of acute and chronic inflammatory diseases, the regulation of IL-8-mediated biological responses is important. Alpha-melanocyte-stimulating hormone (a-MSH), a tridecapeptide, inhibits most forms of inflammation by an unknown mechanism. In the present study, we have found that a-MSH interacts predominantly with melanocortin-1 receptors and inhibits several IL-8-induced biological responses in macrophages and neutrophils. It downregulated receptors for IL-8 but not for TNF, IL-4, IL-13 or TNF-related apoptosisinducing ligand (TRAIL) in neutrophils. It down-regulated CXCR type 1 and 2 but not mRNA levels. a-MSH did not inhibit IL-8 binding in purified cell membrane or affinitypurified CXCR. IL-8 or anti-CXCR Ab protected against a-MSH-mediated inhibition of IL-8 binding. The level of neutrophil elastase, a specific serine protease, but not cathepsin G or proteinase 3 increased in a-MSH-treated cells, and restoration of CXCR by specific neutrophil elastase or serine protease inhibitors indicates the involvement of elastase in a-MSH-induced down-regulation of CXCR. These studies suggest that a-MSH inhibits IL-8-mediated biological responses by down-regulating CXCR through induction of serine protease and that a-MSH acts as a potent immunomodulator in neutrophil-driven inflammatory distress.

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Interleukin-4 Down-regulates Both Forms of Tumor Necrosis Factor Receptor and Receptor-mediated Apoptosis, NF-κB, AP-1, and c-Jun N-Terminal Kinase

Cited by 65 publications

References 40 publications

Interleukin-4 Reversibly Inhibits Osteoclastogenesis via Inhibition of NF-κB and Mitogen-activated Protein Kinase Signaling

Interleukin-4 Reversibly Inhibits Osteoclastogenesis via Inhibition of NF-κB and Mitogen-activated Protein Kinase Signaling

Reprogramming of human postmitotic neutrophils into macrophages by growth factors

α‐melanocyte‐stimulating hormone down‐regulates CXC receptors through activation of neutrophil elastase

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