Effect of Cytokines on Production of Insulin-like Growth Factor Binding Proteins (IGFBPs) from Human Fibroblasts in Culture

Liu, Yanjung; Tsushima, Takahiro; Miyakawa, Megumi; Isozaki, Osamu; Yamada, Hiroki; Xu, Zhang Rong; Iwamoto, Yasuhiko

doi:10.1507/endocrj.46.suppl_s63

Cited by 5 publications

(4 citation statements)

References 11 publications

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“…TNFα and IL-1β. These cytokines have been shown to increase the degradation of IGFBP-3 in fibroblasts in vitro [44]. In addition, several cytokines may be required to increase IGFBP-3 proteolysis.…”

Section: Resultsmentioning

confidence: 99%

Acute Interleukin-6 Infusion Increases IGFBP-1 but Has No Short-Term Effect on IGFBP-3 Proteolysis in Healthy Men

Pihl

Carlsson-Skwirut²,

Berg³

et al. 2006

Horm Res Paediatr

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Human conditions of elevated interleukin-6 (IL-6) and transgenic mice overexpressing IL-6 have increased proteolytic degradation of insulin-like growth factor binding protein (IGFBP)-3. In addition, IL-6 alters the hepatic expression of insulin-like growth factor-I (IGF-I) and the IGFBPs in vitro. The aim of the present study was to investigate whether moderately elevated IL-6 levels have short-term effects on circulating IGF-I, IGFBP-1 and IGFBP-3 proteolysis in vivo. Healthy men received a 3-h IL-6 (n = 6) or saline (n = 6) infusion and blood samples were collected prior to and up to 8 h after the start of infusion. Free IGF-I, total IGF-I, IGFBP-1, insulin and cortisol were measured using immunoassays. Serum IGFBP-3 proteolysis was analyzed by Western immunoblot and by in vitro degradation of ¹²⁵I-IGFBP-3. We found that IL-6 concentrations reaching approximately 100 pg/ml significantly increased IGFBP-1 after the end of infusion in the absence of changes in insulin. In addition, plasma levels of cortisol were increased in response to IL-6 during and after infusion compared to saline. There was no effect of IL-6 on IGFBP-3 proteolysis, total IGF-I or free dissociable IGF-I. These data suggest that moderately elevated levels of IL-6 such as in the post-operative state or after exercise may contribute to increased levels of IGFBP-1. Although this study does not exclude that high levels and/or prolonged exposure to IL-6 may induce IGFBP-3 proteolysis in sepsis or chronic inflammatory disease, it suggests that IL-6 released from exercising skeletal muscle is not directly involved in proteolysis of circulating IGFBP-3.

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Section: Resultsmentioning

confidence: 99%

Acute Interleukin-6 Infusion Increases IGFBP-1 but Has No Short-Term Effect on IGFBP-3 Proteolysis in Healthy Men

Pihl

Carlsson-Skwirut²,

Berg³

et al. 2006

Horm Res Paediatr

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“…It binds with high affinity to IGF2 and inhibits many of its functions, including proliferation and differentiation (Kelley et al, 1996). Its expression has previously been reported to be stimulated by IL-1 and TNF but inhibited by the presence of TGFβ (Martin et al, 1994;Liu et al, 1999), and this might explain the significantly increased levels of IGFBP6 in paucibacillary lesions. In paucibacillary tissues, high IGFBP6 levels could play a role in controlling cellular proliferation by inhibiting IGF2…”

Section: Discussionmentioning

confidence: 98%

Expression profiling reveals differences in immuno-inflammatory gene expression between the two disease forms of sheep paratuberculosis

Smeed

Watkins

Gossner

et al. 2010

Veterinary Immunology and Immunopathology

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Paratuberculosis is a chronic enteropathy of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP); infection of sheep results in two disease forms - paucibacillary (tuberculoid) and multibacillary (lepromatous) associated with the differential polarization of the immune response. In addition the majority of MAP-infected animals show no pathology and remain asymptomatic. Microarray and real-time RT-qPCR analyses were used to compare gene expression in ileum from sheep with the two disease forms and asymptomatic sheep, to further understand the molecular basis of the pathologies. Microarrays identified 36 genes with fold-change of >1.5 and P< or = 0.05 in at least one comparison; eight candidates were chosen for RT-qPCR validation. Sequence analysis of two candidates, CXCR4 and IGFBP6, identified three SNPs in each; five were found in all three forms of disease and showed no significant relationship to pathological type. The IGFBP6 G(3743) A SNP was not detected in asymptomatic sheep. The data show that the two forms of disease are associated with distinct molecular profiles highlighted by the differential expression of chemokine and chemokine receptor transcripts, the protein products of which might be implicated in the different cell infiltrates of the pathologies. The cells within the lesions also show evidence of abnormal activation; they express high levels of cytokine transcripts but have reduced expression levels of transcripts for T cell receptor associated molecules.

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“…After c-Myc activation, the decrease of IGFBP-6 significantly enhances fibroblast activation and mobilization and increases the chemotactic potency of human primary breast cancer fibroblasts. As we have already highlighted, TGF-β has a suppressive role on IGFBP-6 [12,13]. Interestingly, it has been described that TGF-β works as a tumor suppressor during the early phases of the carcinogenesis, while it becomes a later promoter of it, as its overexpression may directly induce tumor metastasis by initiating events necessary for invasion [77,78].…”

Section: Igfbp-6 Controls Fibroblasts and Tme During Cancer Progressionmentioning

confidence: 96%

“…TGF-β and IGFBP-6 have a complex relationship. IGFBP-6 expression has previously been reported to be stimulated by Interleukin-1b and tumor necrosis factor-alpha but inhibited by the presence of TGFβ [12,13]. Indeed, TGF-β inhibits IGFBP-6 expression in osteoblast-enriched cells from fetal rat calvariae, by transcriptional mechanisms [14].…”

Section: Evolution Immunity and Tissue Repairmentioning

confidence: 98%

IGFBP-6: At the Crossroads of Immunity, Tissue Repair and Fibrosis

Liso

Venuto

Coda

et al. 2022

IJMS

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Insulin-like growth factors binding protein-6 (IGFBP-6) is involved in a relevant number of cellular activities and represents an important factor in the immune response, particularly in human dendritic cells (DCs). Over the past several years, significant insights into the IGF-independent effects of IGFBP-6 were discovered, such as the induction of chemotaxis, capacity to increase oxidative burst and neutrophils degranulation, ability to induce metabolic changes in DCs, and, more recently, the regulation of the Sonic Hedgehog (SHH) signaling pathway during fibrosis. IGFBP-6 has been implicated in different human diseases, and it plays a rather controversial role in the biology of tumors. Notably, well established relationships between immunity, stroma activity, and fibrosis are prognostic and predictive of response to cancer immunotherapy. This review aims at describing the current understanding of mechanisms that link IGFBP-6 and fibrosis development and at highlighting the multiple roles of IGFBP-6 to provide an insight into evolutionarily conserved mechanisms that can be relevant for inflammation, tumor immunity, and immunological diseases.

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Effect of Cytokines on Production of Insulin-like Growth Factor Binding Proteins (IGFBPs) from Human Fibroblasts in Culture

Cited by 5 publications

References 11 publications

Acute Interleukin-6 Infusion Increases IGFBP-1 but Has No Short-Term Effect on IGFBP-3 Proteolysis in Healthy Men

Acute Interleukin-6 Infusion Increases IGFBP-1 but Has No Short-Term Effect on IGFBP-3 Proteolysis in Healthy Men

Expression profiling reveals differences in immuno-inflammatory gene expression between the two disease forms of sheep paratuberculosis

IGFBP-6: At the Crossroads of Immunity, Tissue Repair and Fibrosis

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