Comment on “Ym1/2 Promotes Th2 Cytokine Expression by Inhibiting 12/15(S)-Lipoxygenase: Identification of a Novel Pathway for Regulating Allergic Inflammation”

Mabalirajan, Ulaganathan ; Agrawal, Anurag ; Ghosh, Balaram (2009) Comment on “Ym1/2 Promotes Th2 Cytokine Expression by Inhibiting 12/15(S)-Lipoxygenase: Identification of a Novel Pathway for Regulating Allergic Inflammation” The Journal of Immunology, 183 (10). 6039.1-6039. ISSN 0022-1767

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Official URL: http://doi.org/10.4049/jimmunol.0990091

Related URL: http://dx.doi.org/10.4049/jimmunol.0990091

Abstract

We read the article published by Cai et al. in the May 1, 2009 issue of The Journal of Immunology (1) with great interest. The experiments are systematic and unequivocal when seen in isolation. However, there are major conflicts between the discovered proallergic effects of Ym1/2 via inhibition of 12(S)-HETE production by 12/15-lipoxygenase (12/15-LOX) and previous reports. In mouse models of allergic airway inflammation resembling asthma, there is increased expression of 12/15-LOX and 12(S)-HETE (2, 3). In near identical models, Ym1/2 is potently up-regulated. In this context, the in vitro observation by Cai et al. of Ym1/2-mediated inhibition of 12/15-LOX resulting in ∼95% inhibition of 12(S)-HETE production is difficult to understand. It also argues against their findings of 12(S)-HETE-mediated inhibition of eosinophilia and Th2 cytokine production. Interestingly, Cai et al. found a specific reduction in airway eosinophils, a significant increase in the lymphocyte count, and no effect on neutrophils with exogenous 12(S)-HETE. These findings contrast with the well-known chemoattractant (4) and lymphocyte anti-mitogenic properties of 12(S)-HETE (5). Furthermore, we have found that administration of 12/15-LOX inhibitors, such as esculetin (2) and baicalein (our unpublished data), in mouse models of asthma decreased cysteinyl leukotrienes and attenuated asthma features. One of these inhibitors, baicalein, was found by Cai et al. to increase Th2 cytokine prediction in vitro. These discrepancies may relate either to the complexity of the in vivo systems or to peculiarities of the coculture system from which much of their data is derived. Precaution need to be exercised when translating comparatively straightforward in vitro observations into complex in vivo correlates.

Item Type:Article
Source:Copyright of this article belongs to American Association of Immunologists.
ID Code:120863
Deposited On:06 Jul 2021 10:13
Last Modified:06 Jul 2021 10:13

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