Effect of FR167653, a cytokine suppressive agent, on endotoxin-induced disseminated intravascular coagulation

Yamamoto, Norikazu; Sakai, Fumihiko; Yamazaki, Harumi; Nakahara, Kunio; Okuhara, Masakuni

doi:10.1016/s0014-2999(96)00537-7

Cited by 103 publications

(56 citation statements)

References 23 publications

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“…Moreover, FR167653 also inhibited the production of proinflammatory cytokines, including IL-1␤ and TNF-␣, in agreement with the previous observations (Fig. 6) [7]. In this regard, inhibition of COX-2 induction may be due to inhibition of the production of proinflammatory cytokines, because proinflammatory cytokines, including IL-1␤ and TNF-␣, have been shown to induce COX-2 expression by monocytes [11,12,15,32,33].…”

Section: Discussionsupporting

confidence: 91%

“…FR167653 51-[7-(4-fluorophenyl)-1, 2, 3, 4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate6 ( Fig. 1) has been developed as one of a new class of compounds for inhibiting cytokine production and it can act as a protective drug in lipopolysaccharide (LPS)-induced disseminated intravascular coagulation in an animal model [7]. Although the inhibition of prostanoid production by FR167653 is thought to be important in this model, the effect of FR167653 on prostanoid production is not sufficiently understood.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin

Kawano

Ogushi

Tani

et al. 1999

Journal of Leukocyte Biology

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FR167653 E1-C7-(4-fluorophenyl)-1, 2, 3, 4-tetrahydro-8 A4-pyridylB pyrazoro C5-1-cD C1, 2, 4D triazin-2-ylD-2-phenylethanedion sulfate monohydrateF was developed to inhibit proinflammatory cytokine production. However, the effects of FR167653 on prostanoid production are unclear. We investigated the effect of FR167653 on proinflammatory cytokine and prostaglandin APGB production by lipopolysaccharide ALPSB-stimulated human peripheral blood monocytes and alveolar macrophages AAMB from the same individuals, and compared the effects in monocytes and AM. FR167653 inhibited interleukin-1␤ and tumor necrosis factor ␣ production. The effect on PGE 2 production was assessed by four parameters. FR167653 inhibited PGE 2 synthesis and LPS induction of cyclooxygenase activity. Western and Northern blot analyses revealed that LPS induction of cyclooxygenase-2 expression was attenuated by this compound. The suppression in monocytes was greater than that in AM. We concluded that the reduction of LPSinduced PGE 2 synthesis by FR167653 was due to inhibition of cyclooxygenase-2 production. These results show that FR167653 may be therapeutically useful for inhibiting production of both inflammatory cytokines and PG production in inflammatory diseases. J. Leukoc. Biol. 65: 80-86; 1999.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin

Kawano

Ogushi

Tani

et al. 1999

Journal of Leukocyte Biology

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“…On the other hand, FR167653 was first discovered as a potent inhibitor of tumor necrosis factor (TNF)-␣ and interleukin-1␤ production (Yamamoto et al, 1996(Yamamoto et al, , 1997. Recent reports have shown that FR167653 inhibits the activation of p38 MAPK by suppressing the phosphorylation of p38, preferentially in the ␣ isoform, but not in the ␥ isoform Takahashi et al, 2001;Yoshinari et al, 2001).…”

Section: Inhibition Of P38 Activation Attenuates L5 Snl-induced Thermmentioning

confidence: 99%

Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation

Obata¹,

Yamanaka²,

Kobayashi³

et al. 2004

J. Neurosci.

290

208

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To investigate whether activation of mitogen-activated protein kinase (MAPK) in damaged and/or undamaged primary afferents participates in neuropathic pain after partial nerve injury, we examined the phosphorylation of extracellular signal-regulated protein kinase (ERK), p38 MAPK, and c-Jun N-terminal kinase (JNK) in the L4 and L5 dorsal root ganglion (DRG) in the L5 spinal nerve ligation (SNL) model. We first confirmed, using activating transcription factor 3 and neuropeptide Y immunoreactivity, that virtually all L4 DRG neurons are spared from axotomy in this model. In the injured L5 DRG, the L5 SNL induced the activation of ERK, p38, and JNK in different populations of DRG neurons. In contrast, in the uninjured L4 DRG, the L5 SNL induced only p38 activation in tyrosine kinase A-expressing small-to medium-diameter neurons. Intrathecal ERK, p38, and JNK inhibitor infusions reversed SNL-induced mechanical allodynia, whereas only p38 inhibitor application attenuated SNL-induced thermal hyperalgesia. Furthermore, the L5 dorsal rhizotomy did not prevent SNL-induced thermal hyperalgesia. We therefore hypothesized that p38 activation in the uninjured L4 DRG might be involved in the development of heat hypersensitivity in the L5 SNL model. In fact, the treatment of the p38 inhibitor and also anti-nerve growth factor reduced SNL-induced upregulation of brain-derived neurotrophic factor and transient receptor potential vanilloid type 1 expression in the L4 DRG. Together, our results demonstrate that the L5 SNL induces differential activation of MAPK in injured and uninjured DRG neurons and, furthermore, that MAPK activation in the primary afferents may participate in generating pain hypersensitivity after partial nerve injury.

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“…A synthesized low-molecular-weight pyrazolotriazine derivative, FR-167653, is a potent suppressor of TNFand IL-1 production via specific inhibition of p38 MAPK activity 26) . Administration of FR167653 has been shown to exert beneficial effects in animal models of disseminated intravascular coagulation 27) , pulmonary ischemia-reperfusion injury 28) , and glomerulonephritis 29) . In the present study, treatment with a p38 MAPK inhibitor, FR167653, resulted in regression of cardiac hypertrophy and fibrosis and improvement in cardiac inflammation.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Effect of a Combination of Rho-Kinase Inhibitor and P38 MAPK Inhibitor on Cardiovascular Remodeling and Oxidative Stress in Dahl Rats

Takeshima

Kobayashi

Koguchi

et al. 2012

JAT

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Aim: Rho-kinase plays a critical role in various cellular functions. p38 mitogen-activated protein kinase (p38 MAPK) plays a central role in the inflammatory cytokine response to immune challenge. We evaluated the effects of a combination of fasudil, a Rho-kinase inhibitor, and FR167653, a p38 MAPK inhibitor, on cardiovascular remodeling, inflammation, and oxidative stress in Dahl salt-sensitive hypertensive (DS) rats. Methods: DS and Dahl salt-resistant (DR) rats were fed a high-salt diet at 6 weeks of age. Vehicle, fasudil (100 mg/kg per day), FR167653 (2 mg/kg per day), and a combination of fasudil and FR167653 were administered to 6-week-old DS rats for 5 weeks.

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Effect of FR167653, a cytokine suppressive agent, on endotoxin-induced disseminated intravascular coagulation

Cited by 103 publications

References 23 publications

Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin

Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin

Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation

Cardioprotective Effect of a Combination of Rho-Kinase Inhibitor and P38 MAPK Inhibitor on Cardiovascular Remodeling and Oxidative Stress in Dahl Rats

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