Suppression of arthritis by an inhibitor of nitric oxide synthase.

McCartney-Francis, Nancy; Allen, Julie K.; Mizel, Diane; Albina, Jorge E.; Xie, Qiao-wen; Nathan, Carl; Wahl, Sharon M.

doi:10.1084/jem.178.2.749

Cited by 597 publications

(301 citation statements)

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“…NO? has been implicated as a mediator of in¯ammatory arthritis in a model using injected streptococcal cell wall fragments (McCartney-Francis et al, 1993). LPS is synergistic with muramyl dipeptide, a synthetic peptidoglycan monomer analogue, in the inhibition of proteoglycan synthesis in chondrocytes (Ikebe et al, 1993), an effect which may be mediated by NO?…”

Section: Discussionmentioning

confidence: 99%

Signalling and cellular specificity of airway nitric oxide production in pertussis

Flak

Goldman

1999

Cell Microbiol

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SummaryBordetella pertussis, the aetiological agent of whooping cough (pertussis), causes selective destruction of ciliated cells of the human airway mucosa. In a hamster tracheal organ culture model, B. pertussis causes identical cytopathology as does tracheal cytotoxin (TCT), a glycopeptide released by the bacterium. The damage caused by B. pertussis or TCT has been shown to be mediated via nitric oxide (NO?). Using immuno¯uorescence detection of the cytokine-inducible NO synthase (iNOS; NOS type II), we determined that B. pertussis induced epithelial NO? production exclusively within non-ciliated cells. This epithelial iNOS activation could be reproduced by the combination of TCT and endotoxin. However, neither TCT alone nor endotoxin alone was capable of inducing epithelial iNOS. This result mirrors the synergistic activity of TCT and endotoxin exhibited in monolayer cultures of tracheal epithelial cells. Therefore, TCT and endotoxin are both important virulence factors of B. pertussis, combining synergistically to cause the speci®c epithelial pathology of pertussis.

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Section: Discussionmentioning

confidence: 99%

Signalling and cellular specificity of airway nitric oxide production in pertussis

Flak

Goldman

1999

Cell Microbiol

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“…Other investigators have reduced the severity of AIA (28,32,33) and of streptococcal cell wall-induced arthritis (26) in rats using N-methyl-L-arginine, a NOS inhibitor, which suggests a fundamental role for NO pathways in these experimental models (26,28). However, a recent evaluation of several iNOS inhibitors in AIA showed that aminoguanidine was able to suppress the level of urinary nitrate excretion during AIA without a reduction in arthritis severity (32).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, inhibitors of NOS have been shown to suppress arthritis in several animal models (26,28,32,33,35), and increased levels of NO have been found in patients with rheumatoid arthritis (36,37). However, it has not been shown that NO is a requisite component of joint inflammation regardless of the cause of arthritis.…”

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confidence: 99%

“…Recent evaluations of NO synthesis in streptococcal cell wall-induced arthritis (26), A M (27)(28)(29)(30)(31)(32)(33), and MRL-lpdlpr mice (34) showed an association between arthritis, increased N O production, and the induction of NOS (26). Moreover, inhibitors of NOS have been shown to suppress arthritis in several animal models (26,28,32,33,35), and increased levels of NO have been found in patients with rheumatoid arthritis (36,37).…”

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confidence: 99%

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Nitric oxide production during adjuvant‐induced and collagen‐induced arthritis

Cannon

Openshaw

Hibbs

et al. 1996

Arthritis & Rheumatism

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Objective. To investigate the role of nitric oxide (NO) production and NO synthase (NOS) induction during adjuvant-induced arthritis (AIA) and collageninduced arthritis (CIA) in Dark Agouti rats.Methods. Urinary nitrate excretion and immune NOS (iNOS) messenger RNA (mRNA) expression were measured in the joint, lymph node, spleen, and liver tissues following the induction of either AIA or CIA.Results. Urinary nitrate excretion and iNOS mRNA expression increased substantially during joint inflammation in both models of arthritis. However, the increases in urinary nitrate excretion and iNOS mRNA expression observed in the joint, liver, and spleen tissues during AIA were greater than those observed during CIA, although iNOS induction in the lymph nodes was similar for both models. A prior injection with Mycobacterium bovis heat-shock protein resulted in suppression of arthritis and NO production in AIA, but not in CIA.Conclusion. Differences in NO production during AIA versus CIA are a reflection of the fundamental pathophysiologic differences between these 2 models of arthritis. Thus, NO production in these 2 models could not be merely a nonspecific reaction to the adjuvant injection, nor simply a byproduct of local inflammation in the joint.Adjuvant-induced arthritis (AIA) and collageninduced arthritis (CIA) are different models of experi-..Supported by the VA Medical Research Program, the NIH (grants HL-40665 and HL-37615), the Nora Eccles Treadwell Foundation, and a University of Utah Research Grant.Grant W. Cannon, MD, Scott J. Openshaw, BS, John B. Hibbs, Jr., MD, John R. Hoidal, MD, Thomas P. Huecksteadt, Marie M. Griffiths, PhD: VA Medical Center, and the University of Utah, Salt Lake City.Address correspondence to Grant W. Cannon, MD, VAMC (llE), 500 Foothill Drive, Salt Lake City, UT 84148.Submitted for publication September 11, 1995; accepted in revised form May 1, 1996. mental arthritis that are induced by the injection of Freund's complete adjuvant (FCA) (1-12) or type I1 collagen (CII) (13-21), respectively. Although these 2 models have many clinical similarities, fundamental differences in their pathophysiology and genetic control are clearly evident. AIA is a particularly informative model because it predominantly involves T cell-mediated mechanisms (1-8), in contrast to CIA, which requires both humoral (14-20) and cellular immunity (21).Nitric oxide (NO), an unstable radical produced by the action of the enzyme NO synthase (NOS) on 1.-arginine, is a mediator of multiple physiologic functions and may also mediate local inflammation and tissue destruction (22-25). After its production and local action, NO is eventually oxidized to nitrate, which is inactive and excreted in the urine. Urinary nitrate can be reduced to nitrite, which, when measured by the Griess reaction, serves as an indirect measure of NO production (22). The induction of immunehflammatory NOS (iNOS) messenger RNA (mRNA) can be detected by polymerase chain reaction (PCR).Recent evaluations of NO synthesis in streptococcal cell wall...

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“…This form of NOS is Ca¥ independent and, once expressed, produces large amounts of NO which may contribute to the host defence mechanisms and immunoregulation (Grabowski et al 1996(Grabowski et al , 1997Moncada et al 1997). It has been shown that in experimental arthritis induced by a single injection of streptococcal cell wall fragments in rats (McCartney-Francis et al 1993) the expression of inducible nitric oxide synthase (iNOS) gene was increased, and administration of l-NMMA profoundly reduced the joint swelling and distortion of the cartilage. It has been also shown that the levels of 3-nitro-tyrosine, which can be produced by NO-dependent oxidative damage, are elevated in the blood serum and synovial fluid in patients with rheumatoid arthritis (Kaur & Halliwell, 1994).…”

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confidence: 99%