Modulation of macrophage and B cell function by glycosaminoglycans

Wrenshall, Lucile E.; Stevens, R. Brian; Cerra, Frank B.; Platt, Jeffrey L.

doi:10.1002/jlb.66.3.391

Cited by 79 publications

(59 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cellular Effects. GAGs display complex biological activities toward various cells, including lymphocytes, monocytes, dendritic, and stromal cells (10,17,(20)(21)(22)(23). We examined cellular responses to GAGs to identify a correlation with disease development in mice.…”

Section: Resultsmentioning

confidence: 99%

“…Suspensions of mouse splenocytes were prepared from freshly removed mouse spleens and erythrocytes were depleted by ACK lysing buffer (0.15 M NH 4 Cl͞10 mM KHCO 3 ͞0.1 mM Na 2 EDTA, pH 7.2). A portion of splenocytes was fractionated on a nylon wool column to obtain B and T cell-enriched subpopulations (16,17). Splenocytes (2.6 ϫ 10 6 ml Ϫ1 ) and B cell-enriched fractions (1.8 ϫ 10 6 ml Ϫ1 ) were cultured with 20 g⅐ml Ϫ1 of CSA, CSB, CSC, HP, or HA in RPMI medium 1640 (Invitrogen) supplemented with 10% FCS (RPMI 1640-10).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Glycosaminoglycans are a potential cause of rheumatoid arthritis

Wang

Roehrl²

2002

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory disease of connective tissue with unknown etiology. We investigated whether aberrant immune responses to glycosaminoglycans (GAGs), a major component of joint cartilage, joint fluid, and other soft connective tissue, causes this disease. Here we show that injection of GAGs such as hyaluronic acid, heparin, and chondroitin sulfates A, B, and C induce arthritis, tendosynovitis, dermatitis, and other pathological conditions in mice. We developed a technique by staining tissue specimens with fluorochrome-or biotin-labeled GAGs to visualize the direct binding between cells and GAGs. We discovered that inflammatory infiltrates from the affected tissue are dominated by a distinct phenotype of GAG-binding cells, a significant portion of which are CD4 ؉ T cells. GAG-binding cells seem to be expanded in bone marrow of GAG-immunized mice. Furthermore, we identified GAG-binding cells in inflamed synovial tissue of human patients with RA. Our findings suggest that carbohydrate self-antigenic GAGs provoke autoimmune dysfunctions that involve the expansion of GAG-binding cells which migrate to anatomical sites rich in GAGs. These GAG-binding cells might, in turn, promote the inflammation and pathology seen both in our murine model and in human RA.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Glycosaminoglycans are a potential cause of rheumatoid arthritis

Wang

Roehrl²

2002

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Although both types of cells have been shown to produce IL-1␤ upon appropriate stimulation (34,35), the promoter is MNase-insensitive from approximately Ϫ500 to Ϫ100 relative to the transcription start site in resting lymphocytes ( Fig. 2A, dotted bars).…”

Section: The Il-1␤ Promoter Is Accessible In Resting Monocyte Lineagementioning

confidence: 99%

The Interleukin-1β Gene Is Transcribed from a Poised Promoter Architecture in Monocytes

Liang

Zhang

McDevit

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cytokine transcription is usually regulated by transcription factor binding and chromatin remodeling following an inducing signal. By contrast, these data showed the interleukin (IL)-1␤ promoter assembles into a "poised" structure, as evidenced by nuclease accessibility and loss of core histones immediately surrounding the transcription start site. Strikingly, these properties do not change upon transcriptional activation by lipopolysaccharide. Furthermore, association of two key transcriptional activators, PU.1 and C/EBP␤, is robust pre-and post-stimulation indicating the IL-1␤ promoter is packaged into a nontranscribed but poised promoter architecture in cells capable of rapidly inducing IL-1␤. Monocyte stimulation causes recruitment of a third factor, IRF-4, to the IL-1␤ enhancer. PU.1 phosphorylation at a CK2 kinase consensus element is required for this recruitment. We showed that CK2 phosphorylates PU.1, CK2 inhibitors abrogate IL-1␤ induction, and CK2 inducibly associates with the IL-1␤ enhancer. Taken together, these data indicate a novel two-step mechanism for IL-1␤ transcription: 1) formation of a poised chromatin architecture, and 2) phosphorylation of an enhancer-bound factor that recruits other activators. We propose that this poised structure may generally characterize rapidly activated genes.

show abstract

“…Accordingly, it appears unlikely that orally administered CS is systemically distributed to connective tissues, such as cartilage and skin, and that exogenously administered CS directly stimulates chondrocyte synthesis of extracellular matrix components. This suggests that the mechanism of action of exogenously administered CS might be mediated from within the intestinal tract by other systems, such as the immunological system (Wrenshall et al, 1999). Our laboratory has already shown that CS affects and upregulates the in vitro antigenspecific Th1 immune response on murine splenocytes sensitized with ovalbumin (OVA) and that CS suppresses the antigen-specific IgE responses (Sakai et al, 2002a).…”

Section: A New Concept For Explaining the Effect Of Chondroitin Sumentioning

confidence: 99%