Neutrophils-derived peroxynitrite contributes to acute hyperalgesia and cell influx in zymosan arthritis

Bezerra, Mirna Marques; Brain, Susan D.; Girão-Carmona, Virgínia Cláudia Carneiro; Greenacre, Stan; Keeble, Julie; Rocha, Francisco Airton Castro

doi:10.1007/s00210-006-0123-9

Cited by 41 publications

(33 citation statements)

References 40 publications

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“…In the knee joint, zymosan is able to simulate an inflammatory response like that observed in the arthritis development, in which both resident synovial and infiltrated immune cells produce several mediators of inflammation, including nitrogen and oxygen-derived free radicals, cytokines, leukotrienes, and prostaglandins, which have been associated with the degradation of articular cartilage (4,46,47). Frasnelli et al (19) demonstrated that Toll-like receptor (TLR) 2 is the major pathway of proinflammatory signaling in zymosan-induced arthritis in mice.…”

Section: Discussionmentioning

confidence: 99%

Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Kanashiro¹,

Pessini²,

Machado³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Kanashiro A, Pessini AC, Machado RR, Malvar DC, Aguiar FA, Soares DM, Vale ML, Souza GEP. Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats. Am J Physiol Regul Integr Comp Physiol 296: R1631-R1640, 2009. First published February 25, 2009 doi:10.1152/ajpregu.90527.2008.-The present study investigated the febrile response in zymosan-induced arthritis, as well as the increase in PGE2 concentration in the cerebrospinal fluid (CSF), along with the effects of antipyretic drugs on these responses in rats. Zymosan intra-articularly injected at the dose of 0.5 mg did not affect the body core temperature (Tc) compared with saline (control), whereas at doses of 1 and 2 mg, zymosan promoted a flattened increase in Tc and declined thereafter. The dose of 4 mg of zymosan was selected for further experiments because it elicited a marked and long-lasting Tc elevation starting at 3 1/2 h, peaking at 5 1/2 h, and remaining until 10 h. This temperature increase was preceded by a decrease in the tail skin temperature, as well as hyperalgesia and edema in the knee joint. No febrile response was observed in the following days. In addition, zymosan-induced fever was not modified by the sciatic nerve excision. Zymosan increased PGE 2 concentration in the CSF but not in the plasma. Oral pretreatment with ibuprofen (5-20 mg/kg), celecoxib (1-10 mg/kg), dipyrone (60 -240 mg/kg), and paracetamol (100 -200 mg/kg) or subcutaneous injection of dexamethasone (0.25-1.0 mg/kg) dose-dependently reduced or prevented the fever during the zymosan-induced arthritis. Celecoxib (5 mg/kg), paracetamol (150 mg/kg), and dipyrone (120 mg/kg) decreased CSF PGE 2 concentration and fever during zymosan-induced arthritis, suggesting the involvement of PGE2 in this response.

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Section: Discussionmentioning

confidence: 99%

Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Kanashiro¹,

Pessini²,

Machado³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…While NO per se appears to be beneficial to joint homeostasis (5,10,11), the combination of NO with other reactive species, such as the superoxide anion, may result in peroxynitrite formation and subsequent tissue lesion (23). We have recently demonstrated that neutrophils contribute to the formation of peroxynitrite in ZYA (4). Hence, the reduced formation of reactive oxygen species secondary to the reduced neutrophil cell influx may participate in the benefit provided by the A. suum extract in arthritis.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of an Extract fromAscaris suumin Experimental Arthritis Models

Rocha¹,

Leite²,

Pompeu

et al. 2008

Infect Immun

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We investigated the effect of an extract from a helminth (Ascaris suum) in zymosan-induced arthritis (ZYA) or collagen-induced arthritis (CIA). Rats and mice, respectively, received 1 mg and 0.1 mg zymosan intraarticularly (i.a.). Test groups received an A. suum extract either per os (p.o.) or intraperitoneally (i.p.) 30 min prior to i.a. zymosan. Controls received saline. Hypernociception was measured using the articular incapacitation test. Cell influx, nitrite, and cytokine levels were assessed in joint exudates. The synovia and distal femoral extremities were used for histopathology. Cartilage damage was assessed through determining glycosaminoglycan (GAG) content. DBA/1J mice were subjected to CIA. The test group received A. suum extract i.p. 1 day after CIA became clinically detectable. Clinical severity and hypernociception were assessed daily. Neutrophil influx was determined using myeloperoxidase activity. The A. suum extract, either i.p. or p.o., significantly and dose-dependently inhibited cell influx and hypernociception in ZYA in addition to reducing GAG loss and ameliorating synovitis. The A. suum extract reduced i.a. levels of NO, interleukin-1␤ (IL-1␤), and IL-10 but not tumor necrosis factor alpha (TNF-␣) in rats subjected to ZYA while reducing i.a. IL-10, but not IL-1␤ or TNF-␣, levels in mice. Clinically, mice subjected to CIA treated with the A. suum extract had less severe arthritis. Hypernociception, myeloperoxidase activity, and synovitis severity were significantly reduced. These data show that a helminth extract given p.o. protects from arthritis severity in two classical arthritis models. This A. suum effect is species independent and functions orally and parenterally. The results show clinical and structural benefits when A. suum extract is given either prophylactically or therapeutically.

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“…During inflammation, the redox environment surrounding the cells changes due to rapid production of reactive oxygen species. Increased levels of reactive oxygen species are implicated in the etiology of inflammatory hyperalgesia (14,(21)(22)(23)(24). Importantly, TRPV1 was found to be responsible for long sustained thermal hypersensitivity in inflammatory hyperalgesia induced by increased levels of hydrogen peroxide (H 2 O 2 ) (25).…”

mentioning

confidence: 99%

Functional and Structural Divergence in Human TRPV1 Channel Subunits by Oxidative Cysteine Modification

Ogawa

Kurokawa

Fujiwara

et al. 2016

Journal of Biological Chemistry

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Transient receptor potential vanilloid 1 (TRPV1) channel is a tetrameric protein that acts as a sensor for noxious stimuli such as heat and for diverse inflammatory mediators such as oxidative stress to mediate nociception in a subset of sensory neurons. In TRPV1 oxidation sensing, cysteine (Cys) oxidation has been considered as the principle mechanism; however, its biochemical basis remains elusive. Here, we characterize the oxidative status of Cys residues in differential redox environments and propose a model of TRPV1 activation by oxidation. Through employing a combination of non-reducing SDS-PAGE, electrophysiology, and mass spectrometry we have identified the formation of subunit dimers carrying a stable intersubunit disulfide bond between Cys-258 and Cys-742 of human TRPV1 (hTRPV1). C258S and C742S hTRPV1 mutants have a decreased protein half-life, reflecting the role of the intersubunit disulfide bond in supporting channel stability. Interestingly, the C258S hTRPV1 mutant shows an abolished response to oxidants. Mass spectrometric analysis of Cys residues of hTRPV1 treated with hydrogen peroxide shows that Cys-258 is highly sensitive to oxidation. Our results suggest that Cys-258 residues are heterogeneously modified in the hTRPV1 tetrameric complex and comprise Cys-258 with free thiol for oxidation sensing and Cys-258, which is involved in the disulfide bond for assisting subunit dimerization. Thus, the hTRPV1 channel has a heterogeneous subunit composition in terms of both redox status and function.

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Neutrophils-derived peroxynitrite contributes to acute hyperalgesia and cell influx in zymosan arthritis

Cited by 41 publications

References 40 publications

Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Characterization and pharmacological evaluation of febrile response on zymosan-induced arthritis in rats

Protective Effect of an Extract fromAscaris suumin Experimental Arthritis Models

Functional and Structural Divergence in Human TRPV1 Channel Subunits by Oxidative Cysteine Modification

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