Interleukin-4 (IL-4) and IL-13 Enhance the Effect of IL-1β on Production of IL-1 Receptor Antagonist by Human Primary Hepatocytes and Hepatoma HepG2 Cells: Differential Effect on C-Reactive Protein Production

Gabay, Cem; Porter, Barbara J.; Guenette, Denis; Billir, Bahri; Arend, William P.

doi:10.1182/blood.v93.4.1299

Cited by 59 publications

(19 citation statements)

References 33 publications

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“…Synergistic interactions of IL-13 and IL-1β have been previously reported to result in increased eotaxin release and decreased RANTES production in human airway smooth muscle cells (35). Similarly, IL-13 was reported to enhance the stimulatory effect of IL-1β on induction of IL-1 receptor antagonist in human hepatoma HepG2 cells (36). Both IL-13 and IL-1β are detectable in elevated concentrations during the progression of allergic asthma (2,37).…”

Section: Discussionmentioning

confidence: 91%

IL‐13 and IL‐1β promote lung fibroblast growth through coordinated up‐regulation of PDGF‐AA and PDGF‐Rα

et al. 2004

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Peribronchiolar fibrosis is a prominent feature of airway remodeling in asthma and involves fibroblast growth and collagen deposition. Interleukin-13 (IL-13), a T-helper 2 cytokine, is a key mediator of airway remodeling in asthma, yet the mechanism through which IL-13 promotes fibroblast growth has not been investigated. In this study, we show that IL-13 stimulates the mitogenesis of mouse, rat, and human lung fibroblasts through release of a soluble mitogen that we identified as PDGF-AA. The IL-13-induced growth of human lung fibroblasts was attenuated by an anti-PDGF-AA neutralizing antibody, and IL-13 stimulated human lung fibroblasts to secrete PDGF-AA. Fibroblasts derived from mouse embryos possessing the lethal Patch mutation, which lack the PDGF-Ralpha, showed no mitogenic response to IL-13. However, Patch cells did exhibit IL-13-induced STAT-6 phosphorylation. Stable transfection of the PDGF-Ralpha into Patch cells restored the growth response to PDGF-AA and IL-13. Through the use of lung fibroblasts from STAT-6-deficient mice, we showed that IL-13-induced PDGF-AA release is STAT-6 dependent, but PDGF-AA-induced growth is STAT-6 independent. Finally, we showed that IL-1beta enhanced IL-13-induced mitogenesis of rat lung fibroblasts through up-regulation of the PDGF-Ralpha. Our findings indicate that IL-13 acts in synergy with IL-1beta to stimulate growth by coordinately up-regulating PDGF-AA and the PDGF-Ralpha, respectively.

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Section: Discussionmentioning

confidence: 91%

IL‐13 and IL‐1β promote lung fibroblast growth through coordinated up‐regulation of PDGF‐AA and PDGF‐Rα

et al. 2004

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“…Studies have shown that relaxation can modulate the immune response, for example, by increasing the number of CD4-positive T cells [ 66 ]. These cells are a source of IL-4 that promotes the production of Th2 cytokines and they stimulate the production of IL-1ra from stimulated monocytes and hepatocytes [ 67 ]. One may speculate that this perhaps could be a possible mechanism to the increase of IL-1ra in the active control group.…”

Section: Discussionmentioning

confidence: 99%

Plasma Cytokine Levels in Fibromyalgia and Their Response to 15 Weeks of Progressive Resistance Exercise or Relaxation Therapy

Ernberg

Christidis

Ghafouri

et al. 2018

Mediators of Inflammation

110

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The aims of this study were to compare circulating cytokines between FM and healthy controls and to investigate the effect on cytokine levels by 15 weeks of progressive resistance exercise or relaxation therapy in FM. Baseline plasma cytokine levels and clinical data were analyzed in 125 women with FM and 130 age-matched healthy women. The FM women were then randomized to progressive resistance exercise (n = 49) or relaxation (n = 43). Baseline IL-2, IL-6, TNF-α, IP-10, and eotaxin were higher in FM than in healthy controls (P < 0.041), whereas IL-1β was lower (P < 0.001). There were weak correlations between cytokine levels and clinical variables. After both interventions, IL-1ra had increased (P = 0.004), while IL-1β had increased in the relaxation group (P = 0.002). Changes of IFN-γ, IL-2, IL-4, IL-6, IL-8, and IL-17A were weakly correlated with changes of PPT, but there were no significant correlations between changes of cytokine and changes in other clinical variables. The elevated plasma levels of several cytokines supports the hypothesis that chronic systemic inflammation may underlie the pathophysiology of FM even if the relation to clinical variables was weak. However, 15 weeks of resistance exercise, as performed in this study, did not show any anti-inflammatory effect on neither FM symptoms nor clinical and functional variables. This trial is registered with ClinicalTrials.gov NCT01226784, registered October 21, 2010. The first patient was recruited October 28, 2010.

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“…RNase protection assays. Using an approach recently described for human IL‐1Ra mRNA (17), a riboprobe was created that would distinguish between the 2 major IL‐1Ra mRNA isoforms (sIL‐1Ra and icIL‐1Ra1) as 2 different protected‐size products following RNase treatment. RT‐PCR was performed on total RNA from LPS‐stimulated murine peritoneal macrophages, using a forward primer specific for the icIL‐1Ra1 sequence 5′ IL‐1Ra (GCA‐TGA‐ATT‐CAG‐GGG‐CAG‐TTC‐CAC‐CCT‐GGG‐AAG‐GT) and a reverse primer complementary to the common sequence 3′ IL‐1Ra (GCA‐TAA‐GCT‐TCT‐GGA‐GCT‐TGA‐TAT‐CAT‐CTC‐CAG).…”

Section: Methodsmentioning

confidence: 99%

Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: A possible role in the resolution of arthritis

Gabay¹,

Marinova-Mutafchieva²,

Williams³

et al. 2001

Arthritis & Rheumatism

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Objective To examine the patterns of production of interleukin‐1 receptor antagonist (IL‐1Ra) isoforms and of IL‐1β during arthritis in vivo. Methods Arthritis was induced in DBA/1 mice by immunization with type II collagen, and the production of IL‐1Ra isoforms was examined in whole joints and in dissected synovial tissues by reverse transcription–polymerase chain reaction (RT‐PCR), RNase protection assay, Western blotting, immunostaining, and in situ hybridization. Production of IL‐1β also was examined using similar approaches. Results Production of IL‐1Ra increased in the joints during collagen‐induced arthritis (CIA). By RT‐PCR, secreted IL‐1Ra messenger RNA (mRNA) was detected in normal joints, whereas intracellular IL‐1Ra type I (icIL‐1Ra1) mRNA was only produced in inflamed joints. Western blot studies showed that icIL‐1Ra1 protein levels increased in the joints during the course of CIA and that icIL‐1Ra3 protein was also present in low amounts. RNase protection assays showed that the IL‐1β:IL‐1Ra mRNA ratio was increased in inflamed joints through day 14 of arthritis, whereas a reverse pattern was present at later time points (from day 20 to day 60). Consistent with this finding, immunohistochemistry and in situ hybridization studies confirmed that icIL‐1Ra1 was only present in inflamed joints. The histologic evaluation of CIA during the course of the disease indicated a resolution of acute inflammation, since icIL‐1Ra1 production increased and the ratio of IL‐1β to total IL‐1Ra decreased. Conclusion Production of IL‐1Ra isoforms, particularly icIL‐1Ra1, is stimulated in inflamed joints during CIA in mice. The combination of decreased production of IL‐1β and elevated levels of icIL‐1Ra1 during the course of CIA was associated with a reduction in inflammatory activity. These results suggest that icIL‐1Ra1 may play a role in the resolution of murine CIA.

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Interleukin-4 (IL-4) and IL-13 Enhance the Effect of IL-1β on Production of IL-1 Receptor Antagonist by Human Primary Hepatocytes and Hepatoma HepG2 Cells: Differential Effect on C-Reactive Protein Production

Cited by 59 publications

References 33 publications

IL‐13 and IL‐1β promote lung fibroblast growth through coordinated up‐regulation of PDGF‐AA and PDGF‐Rα

IL‐13 and IL‐1β promote lung fibroblast growth through coordinated up‐regulation of PDGF‐AA and PDGF‐Rα

Plasma Cytokine Levels in Fibromyalgia and Their Response to 15 Weeks of Progressive Resistance Exercise or Relaxation Therapy

Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: A possible role in the resolution of arthritis

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