Cytokine Regulation of the Immune Response: An in Vivo Model

Hines, Keith L.; Christ, Marielle; Wahl, Sharon M.

doi:10.1006/immu.1993.1035

Cited by 10 publications

(13 citation statements)

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“…Thymus and spleen were removed from littermates with a wild-type (+/+), heterozygous (+/-), or null (-/-) TGF-(31 genotype, and single-cell suspensions were prepared as described (22 (26)(27)(28). FN polypeptides containing the arginylglycylaspartic acid (RGD) domain, the alternatively spliced connecting segment (CS-1), and two nonoverlapping sequences corresponding to the FN-C/H region (FN-C/H-I, Tyr-Glu-Lys-Pro-Gly-Ser-ProPro-Arg-Glu-Val-Val-Pro-Arg-Pro-Arg-Gly-Val; FN-C/ H-V, Trp-Gln-Pro-Pro-Arg-Ala-Arg-Ile) were synthesized and purified as described (26,27).…”

mentioning

confidence: 99%

Synthetic fibronectin peptides interrupt inflammatory cell infiltration in transforming growth factor beta 1 knockout mice.

Hines

Kulkarni

McCarthy

et al. 1994

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

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confidence: 99%

Synthetic fibronectin peptides interrupt inflammatory cell infiltration in transforming growth factor beta 1 knockout mice.

Hines

Kulkarni

McCarthy

et al. 1994

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

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“…Peripheral arthritis was initiated in genetically susceptible female Lewis rats (Charles River Breeding Laboratories, Wilmington, MA) by a single ip injection of group A SCW peptidoglycanpolysaccharide complexes (Lee Laboratories, Grayson, GA) as previously described (16). The severity of arthritis was monitored by clinical scoring of each ankle and wrist joint with the articular index (AI), which measures the degree of swelling, erythema, and distortion (0 ϭ normal, 1 ϭ slight, 2 ϭ moderate, 3 ϭ pronounced, 4 ϭ severe inflammation).…”

Section: Arthritis Induction and Hcg Administrationmentioning

confidence: 99%

“…Rat joints fixed with 10% neutral buffered formalin for at least 24 hours were embedded in paraffin after decalcification in 10% EDTA, sectioned (7 m), and stained with hematoxylin and eosin. For immunohistochemical staining, the sections were stained using a peroxidase Vectastain Elite ABC kit (Vector Laboratories, Burlingame, CA) (16). Polyclonal rabbit anti-mouse inducible nitric oxide (NO) synthase (iNOS) antibody was obtained from Upstate Biotechnology (Lake Placid, NY) and used at a 1:200 dilution.…”

Section: Arthritis Induction and Hcg Administrationmentioning

confidence: 99%

“…Based on the suggested association between pregnancy, HCG production, and diminished signs and symptoms of arthritis, we sought, in this study, to directly assess the effectiveness of systemic administration of clinical-grade HCG in altering the progression of streptococcal cell wall (SCW)-induced arthritis in rats. In this model, a single intraperitoneal (ip) injection of SCW in genetically susceptible female Lewis rats initiates an acute inflammation in the peripheral joints, followed by a remission phase and the development of a chronic proliferative and erosive joint disease that resembles human RA (16,17). Daily administration of clinical-grade HCG, in doses sufficient to achieve blood levels of HCG comparable to those found in early pregnancy (18), was initiated preceding the injection of an arthritogenic dose of SCW.…”

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Suppression of streptococcal cell wall–induced arthritis by human chorionic gonadotropin

Song

Zeng

Jin

et al. 2000

Arthritis & Rheumatism

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“…While not a model of TMD, this arthritis model is characterized by acute and chronic synovial inflammation and tissue damage and provides insight into cellular and molecular pathways which underlie joint pathology. Intraperitoneal delivery of peptidoglycan-polysaccharide components of the cell walls of group A streptococci results in dissemination of the bacterial products to three primary target tissues, the spleen, liver and peripheral joints [Hines et al, 1993;McCartney-Francis et al, 1993]. Deposition of these proinflammatory, immunogenic and degradation-resistant bacterial constituents in the peripheral joints results in a rapid inflammatory response in the synovium, with adhesion, recruitment and infiltration of leukocytes, local release of inflammatory mediators, and tissue swelling.…”

Section: Experimental Model Of Joint Pathologymentioning

confidence: 99%

Nitric Oxide in Experimental Joint Inflammation

Wahl

McCartney-Francis

Chan

et al. 2003

Cells Tissues Organs

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The host response to infection or injury initiates a cascade of events involving recruitment of leukocytes and the release of multiple inflammatory mediators. One of these mediators, nitric oxide (NO), not only represents an important microbicidal agent in host defense, but also functions as a biological signaling and effector molecule in inflammation and immunity. However, overproduction of NO can be autotoxic and contribute to tissue damage and has been implicated in pathogenesis of tumors, and infectious, autoimmune and chronic degenerative diseases. NO is generated via constitutive and inducible nitric oxide synthases (iNOS) which catalyze the oxidation of a guanidino nitrogen associated with L-arginine. Whereas endothelial NOS (eNOS) and neuronal NOS (nNOS) are constitutively expressed, iNOS is transcriptionally induced by bacterial constituents and inflammatory mediators, including TNFα and IL-1. In an experimental model of bacterial component-induced joint inflammation and tissue degradation, functionally distinct roles of the constitutive NOS and iNOS were demonstrated. Following systemic delivery of an arthritogenic dose of streptococcal cell walls (SCW), these bacterial peptidoglycan-polysaccharide complexes disseminate and target the peripheral joints, liver and spleen of the treated animals. Following deposition of the SCW in the peripheral joints, an initial innate inflammatory response to the bacterial components progresses into an adaptive immune response with the recruitment and activation of mononuclear phagocytes and T lymphocytes. With the release of cytokines and inflammatory mediators, there is an upregulation of gene expression for iNOS, but not the constitutive nNOS or eNOS. Nonetheless, the constitutive NOS isoforms, regulated by calcium fluxes and interaction with calmodulin, may also enhance NO production. Increased release of NO was detected not only in the synovium, but also in the circulation, and plasma levels of nitrate plus nitrite, the stable products of NO reactions, correlated with disease progression. Following inhibition of NO production with nonspecific NOS inhibitors, such as N^G-monomethyl-L-arginine, which target all three isoforms, there is a striking therapeutic benefit with reduced signs and symptoms of erosive arthritis. In contrast, selective targeting of iNOS with N-iminoethyl-L-lysine resulted in exacerbation of the synovial inflammation and degradation of joint structures. Based on these data, it appears that the constitutive isoforms of NOS contribute to the pathophysiology of the arthropathy, and that induced NOS and NO may function, in part, in a protective pathway. Moreover, the suppression of NO following treatment with TNFα antagonists results in reduced inflammation and the associated synovial pathology. Collectively, these data implicate discrete roles for the NOS isoforms in the emergence of local tissue pathology and underscore the need to define the specific pathways that are being targeted for interventional strategies.

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Cytokine Regulation of the Immune Response: An in Vivo Model

Cited by 10 publications

References 0 publications

Synthetic fibronectin peptides interrupt inflammatory cell infiltration in transforming growth factor beta 1 knockout mice.

Synthetic fibronectin peptides interrupt inflammatory cell infiltration in transforming growth factor beta 1 knockout mice.

Suppression of streptococcal cell wall–induced arthritis by human chorionic gonadotropin

Nitric Oxide in Experimental Joint Inflammation

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