Involvement of leukotriene B4 in arthritis models

Tsuji, Fumio; Oki, Kenji; Fujisawa, Kotaro; Okahara, Akihiko; Horiuchi, Masato; Mita, Shiro

doi:10.1016/s0024-3205(98)00556-6

Cited by 25 publications

(20 citation statements)

References 13 publications

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“…Independent studies with two other LTB 4 receptor antagonists also yielded similar results in IL-1α accelerated CIA model [34]. In an LPS accelerated CIA model, use of a FLAP inhibitor SA6541 reduced the severity of disease [35]. Studies in mice deficient in the LTB 4 pathway quickly followed the antagonist experiments.…”

Section: Role Of Leukotriene B 4 Receptors In Arthritismentioning

confidence: 74%

Role of leukotriene B4 receptors in rheumatoid arthritis

Mathis

Jala

Haribabu

2007

Autoimmunity Reviews

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The purpose of this review is to summarize the role that murine models of arthritis are playing in the understanding of human rheumatoid arthritis and how leukotriene B 4 (LTB 4 ) is emerging as an important target in this field. Both the collagen-induced arthritis (CIA) model and the K/BxN serum transfer arthritis model have contributed to outline the potential mechanisms involved in inflammatory arthritis. Indeed, the CIA model has contributed to the development of effective anti-TNF and anti-IL-1β based treatments for RA that are currently in the clinic. Many recent studies in mouse models have suggested a critical role for LTB 4 and its receptors in the development of inflammatory arthritis. Inhibitors of LTB 4 biosynthesis as well as LTB 4 receptors are protective in mouse models of RA and mice deficient in the LTB 4 biosynthetic enzymes or LTB 4 receptors are resistant to disease development suggesting several promising targets for RA in this pathway. KeywordsRheumatoid Arthritis; Leukotriene B4 receptors; arthritis mouse models; FLAP Take home message• Mouse models of RA have provided a great deal of information on the mechanisms involved in human RA and led to the development of effective therapies and are likely to uncover additional therapeutic opportunities • Chemoattractants and cytokines form important amplification loops for perpetual joint inflammation in RA • Inhibition of inflammatory cell recruitment to the rheumatoid synovium represents a potential target for RA treatment.• LTB 4 and its receptors play a critical role in the recruitment of leucocytes to the inflammatory sites. Mice lacking either the enzymes involved in LTB 4 biosynthesis or the LTB 4 receptors are completely protected from the development of RA.• Unraveling the mechanisms of LTB 4 /BLT1 and LTB 4 /BLT2 axis and structure/ function of BLT1 and BLT2 will provide important insights into identification of novel and dual antagonists for blocking their function.

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Section: Role Of Leukotriene B 4 Receptors In Arthritismentioning

confidence: 74%

Role of leukotriene B4 receptors in rheumatoid arthritis

Mathis

Jala

Haribabu

2007

Autoimmunity Reviews

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“…SA6541 showed good oral anti-inflammatory activities at doses exceeding 50 mg/kg in mice. [7][8][9] SA6541 also inhibited human LTA 4 hydrolase (IC 50 ϭ25 nM, unpublished data). In the present study, we investigated the role of LTB 4 in 5-lipoxygenase metabolite-and allergy-induced itch-associated responses in mice using SA6541 at a dose of 100 mg/kg.…”

mentioning

confidence: 84%

Role of Leukotriene B4 in 5-Lipoxygenase Metabolite- and Allergy-Induced Itch-Associated Responses in Mice

Tsuji

Aono

Tsuboi

et al. 2010

Biological & Pharmaceutical Bulletin

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We investigated the role of leukotriene (LT) B 4 in 5-lipoxygenase metabolite-and allergy-induced itch-associated responses using SA6541, an LTA 4 hydrolase inhibitor. Itch-associated responses were induced by intradermal injection of 5-hydroperoxyeicosatetraenoic acid (HPETE), a precursor of 5-lipoxygenase metabolites, and passive cutaneous anaphylaxis in ICR mice. By screening molecules related to arachidonic acid metabolism or pruritus, SA6541 was found to be a specific inhibiter of LTA 4 hydrolase. Pharmacokinetic studies confirmed the specificity of SA6541 at an oral dose of 100 mg/kg in mice. 5-HPETE induced scratching behavior, which was inhibited by SA6541 (100 mg/kg). However, SA6541 (100 mg/kg) hardly attenuated the 5-HPETE-induced increase in vascular permeability. Moreover, SA6541 (100 mg/kg) partially attenuated scratching behavior, but did not affect the increase in vascular permeability caused by passive cutaneous anaphylaxis. On the other hand, ketotifen fumarate, a histamine H1 antagonist, strongly inhibited the scratching behavior and the increase in vascular permeability caused by passive cutaneous anaphylaxis. These results suggest that LTB 4 is an endogenous itch mediator in the skin and is involved in the pruritus response in allergic reactions.

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“…Although the distribution of 5-lipoxygenase is restricted to certain myeloid cells, LTB 4 is secreted by other cells because the enzymes capable of catalyzing the conversion of LTB 4 to other leukotrienes are widely distributed in tissues [10,20]. In fact LTB 4 has been identi®ed in in¯ammatory exudates in arthritis [142] and cystic ®brosis [71] and in the epidermis of patients with psoriasis [141]. Leukotrienes C 4 -D 4 -E 4 have also been identi®ed in several models of in¯ammation, in particular, hypersensitivity disorders such as asthma [61].…”

Section: Lipoxygenase Systemmentioning

confidence: 99%

Essential fatty acids and the brain: possible health implications

Youdim

Martín

Joseph

2000

Intl J of Devlp Neuroscience

428

273

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Linoleic and a-linolenic acid are essential for normal cellular function, and act as precursors for the synthesis of longer chained polyunsaturated fatty acids (PUFAs) such as arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), which have been shown to partake in numerous cellular functions aecting membrane¯uidity, membrane enzyme activities and eicosanoid synthesis. The brain is particularly rich in PUFAs such as DHA, and changes in tissue membrane composition of these PUFAs re¯ect that of the dietary source. The decline in structural and functional integrity of this tissue appears to correlate with loss in membrane DHA concentrations. Arachidonic acid, also predominant in this tissue, is a major precursor for the synthesis of eicosanoids, that serve as intracellular or extracellular signals. With aging comes a likely increase in reactive oxygen species and hence a concomitant decline in membrane PUFA concentrations, and with it, cognitive impairment. Neurodegenerative disorders such as Parkinson's and Alzheimer's disease also appear to exhibit membrane loss of PUFAs. Thus it may be that an optimal diet with a balance of n-6 and n-3 fatty acids may help to delay their onset or reduce the insult to brain functions which these diseases elicit. Published by Elsevier Science Ltd.

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Involvement of leukotriene B4 in arthritis models

Cited by 25 publications

References 13 publications

Role of leukotriene B4 receptors in rheumatoid arthritis

Role of leukotriene B4 receptors in rheumatoid arthritis

Role of Leukotriene B4 in 5-Lipoxygenase Metabolite- and Allergy-Induced Itch-Associated Responses in Mice

Essential fatty acids and the brain: possible health implications

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