Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

Jung, Mechthild; Sabat, Robert; Krätzschmar, Jörn; Seidel, Henrik; Wolk, Kerstin; Schönbein, Christiane; Schütt, Sabine; Friedrich, Markus; Döcke, Wolf‐Dietrich; Asadullah, Khusru; Volk, Hans‐Dieter; Grütz, Gerald

doi:10.1002/eji.200324323

Cited by 80 publications

(98 citation statements)

References 36 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, monocytes do express antigenic HO-1 and further increase its expression when treated for 24 h with IL-10, whereas LPS inhibits the effect of IL-10 ( Fig. 2B), substantiating recent data [23,24]. Because recent findings have proposed that IL-10-induced Bcl-3 is required for suppression of TNF-a production in murine macrophages [25], we also explored whether antigenic Bcl-3 could be induced by IL-10 under our experimental conditions.…”

Section: Resultssupporting

confidence: 90%

“…The data also exclude HO-1 and/or Bcl-3 as potential mediators of the IL-10-mediated effects of IL-10 in human neutrophils. These latter findings are consistent with the lack of correlation between the expression or activity of HO-1 and the anti-inflammatory effects of IL-10 recently observed in human monocytes [23,24], but are in contrast with the identification of Bcl-3 as an IL-10-inducible molecule responsible for the suppression of LPS-induced TNF-a production in murine macrophages [25]. Species-specific characteristics might partially explain these contrasting findings.…”

Section: Resultssupporting

confidence: 88%

See 1 more Smart Citation

Lipopolysaccharide primes neutrophils for a rapid response to IL-10

et al. 2005

View full text Add to dashboard Cite

Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 88%

Lipopolysaccharide primes neutrophils for a rapid response to IL-10

et al. 2005

View full text Add to dashboard Cite

“…However, IL-10 has been found to stimulate the phagocytosis of apoptotic cells by monocytes and macrophages 53,54 , and GAS6 and MER are among the monocyte genes that are upregulated by IL-10 (REF. 55 ).Apoptotic cells appear to exert their immunosuppressive effect on DCs through a TAM signal transduction pathway that is similar to that outlined earlier for the inhibition of inflammation. The prior addition of apoptotic cells to cultured DCs, for example, has been shown to inhibit both LPS-induced NF-κB activation and secretion of TNF and IL-12, and this inhibition has been found to depend on and be transduced through MER 56,57 .…”

mentioning

confidence: 63%

Section: Tam Regulation Of Phagocytosismentioning

confidence: 99%

Immunobiology of the TAM receptors

2008

View full text Add to dashboard Cite

Recent studies have revealed that the TAM receptor protein tyrosine kinases -TYRO3, AXL and MER -have pivotal roles in innate immunity. They inhibit inflammation in dendritic cells and macrophages, promote the phagocytosis of apoptotic cells and membranous organelles, and stimulate the maturation of natural killer cells. Each of these phenomena may depend on a cooperative interaction between TAM receptor and cytokine receptor signalling systems. Although its importance was previously unrecognized, TAM signalling promises to have an increasingly prominent role in studies of innate immune regulation.Receptor protein tyrosine kinases (PTKs) are cell-surface transmembrane receptors that contain a regulated PTK activity within their cytoplasmic domains. They function as sensors for extracellular ligands, the binding of which triggers receptor dimerization and activation of the receptor's kinase. This leads to the recruitment, phosphorylation and activation of multiple downstream signalling proteins, which ultimately change the physiology of cells. Although there are only 58 receptor PTK genes in the human genome 1 (see the human kinome website), the signal transduction cascades initiated by receptor PTK activation control diverse cellular processes -from cell differentiation to cell death. Well-known receptor PTK subfamilies include the ERBB receptors, which have essential roles in cardiac and neural development and the progression of some forms of breast cancer 2 ; and the ephrin receptors, which are required for tissue morphogenesis and the patterning of neuronal connections in the developing brain 3 .The focus of this Review, the TAM group, was among the last receptor PTK subfamilies to be identified, and the biological roles of its three members -TYRO3, AXL and MERremained uncharacterized for several years. Largely through the analysis of engineered lossof-function mutants in mice, these roles have become increasingly apparent. They reflect a specific requirement for TAM signalling in settings in which fully differentiated cells, tissues and organs must be maintained in the face of continuous challenge, turnover and renewal. In humans, ongoing homeostatic regulation of this sort must be carried out, frequently on a daily basis, for decades. Although an essential role for TAM regulation of tissue homeostasis is evident in the adult nervous, reproductive and vascular systems, it is in In this Review, we highlight the central roles that TAM signalling has in the intrinsic inhibition of the inflammatory response to pathogens by dendritic cells (DCs) and macrophages; during phagocytosis of apoptotic cells by these same cells; and in the maturation and killing activity of natural killer (NK) cells. We also discuss how, in many or all of these settings, TAM receptors depend on and interact with cytokine receptors. TAM receptors and ligandsThe three TAM receptors, TYRO3, AXL and MER, were identified as a distinct receptor PTK subfamily in 1991 (REFS 4,5 ). Subsequent cloning of full-length cDNAs by multiple labo...

show abstract

“…In addition, exogenous administration of HO-1 increases IL-10 production in macrophages, which leads to the resolution of neutrophilic migration in the lung after lipopolysaccharide administration (36). In contrast, HO-1 does not seem to play a significant role in the antiinflammatory activity of IL-10 in human monocytes or macrophages (37,38), and an autoregulatory feedback loop is present in lipopolysaccharide-stimulated human monocytes, involving proinflammatory cytokines and IL-10 (39), with a likely predominant role of TNF␣ (40). Further studies would be necessary to establish whether the inhibitory effects of CoPP on IL-10 may be the result of interference with feedback mechanisms driven by TNF␣ or the consequence of immunosuppressive effects on Th2 cells.…”

Section: Discussionmentioning

confidence: 99%

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Devesa¹,

Ferrándiz²,

Terencio³

et al. 2005

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Heme oxygenase 1 (HO-1) can be induced by inflammatory mediators as an adaptive response. The objective of the present study was to determine the consequences of HO-1 modulation in the murine collagen-induced arthritis (CIA) model.Methods. DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 22 to day 29 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, joints were examined for histopathologic changes. Cytokine levels in paws were measured by enzyme-linked immunosorbent assay. Levels of HO-1, cyclooxygenase 2 (COX-2), and prostaglandin E 2 (PGE 2 ) were determined. Effects of treatments on the early phase of disease and after prophylactic administration were also assessed.Results. CoPP strongly induced HO-1, resulting in the inhibition of cartilage erosion accompanied by extensive fibrosis in the joint. Levels of tumor necrosis factor ␣ (TNF␣), interleukin-2 (IL-2), and IL-10 were inhibited by CoPP, whereas levels of vascular endothelial growth factor were increased. Treatment with SnPP significantly reduced the severity of CIA, with inhibition of joint inflammation and cartilage destruction. The levels of PGE 2 , IL-1␤, and TNF␣ were also significantly reduced by SnPP treatment, which did not modify COX-2 protein expression. SnPP was more effective than CoPP in preventing the development of CIA (prophylactic administration).Conclusion. HO-1 is induced during CIA. Although overexpression of this protein causes some beneficial effects, strategies aimed at HO-1 overexpression cannot slow the progression of the chronic inflammatory disease, whereas treatment with SnPP, which inhibits HO-1, exerts prophylactic and therapeutic effects.

show abstract

Expression profiling of IL‐10‐regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL‐10 therapy

Cited by 80 publications

References 36 publications

Lipopolysaccharide primes neutrophils for a rapid response to IL-10

Lipopolysaccharide primes neutrophils for a rapid response to IL-10

Immunobiology of the TAM receptors

Influence of heme oxygenase 1 modulation on the progression of murine collagen‐induced arthritis

Contact Info

Product

Resources

About