Leukotriene B4-Driven Neutrophil Recruitment to the Skin Is Essential for Allergic Skin Inflammation

Oyoshi, Michiko K.; He, Rui; Li, Yitang; Mondal, Subhanjan; Yoon, Jeong‐Won; Afshar, Roshi; Chen, Mei; Lee, David M.; Luo, Hongbo; Luster, Andrew D.; Cho, John S.; Miller, Lloyd S.; Larson, Allison R.; Murphy, Gëorge F.; Geha, Raif S.

doi:10.1016/j.immuni.2012.06.018

Cited by 174 publications

(151 citation statements)

References 37 publications

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“…20, 21 Neutrophil recruitment is a hall mark of innate immune responses, 22 and innate recruitment of neutrophil to the skin through leukotriene B4 (LTB4) is critical for induction of subsequent allergic skin inflammation. 22, 23 We recently reported that RWPE challenge induces CXCR2 and TLR4-dependent innate recruitment of activated neutrophils to the airways, and these recruited neutrophil are critical for induction of allergic sensitization and allergic airway inflammation. 6 In the present study, we extend our earlier observations by demonstrating a broad role of MD2 in induction of innate and allergic airway inflammation and allergic sensitization by CDE, RWPE and extracts of pollens from grasses, weeds and trees.…”

Section: Discussionmentioning

confidence: 99%

“…29 This MD2/TLR4-induced innate neutrophil recruitment facilitates allergic sensitization and allergic airway inflammation. 6, 23 …”

Section: Discussionmentioning

confidence: 99%

“…If proven correct, additional carefully conducted mechanistic studies will be required to determine whether these recruited neutrophils contribute to severe asthma and sudden-onset fatal asthma by stimulating allergic sensitization and allergic inflammation. 6, 23 …”

Section: Discussionmentioning

confidence: 99%

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Myeloid differentiation protein 2 facilitates pollen- and cat dander–induced innate and allergic airway inflammation

Hosoki

Boldogh

Aguilera-Aguirre

et al. 2016

Journal of Allergy and Clinical Immunology

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Background The NHANES study identified several pollens and cat dander among the most common allergens that induce allergic sensitization and allergic diseases. We recently reported that ragweed pollen extract (RWPE) requires TLR4 to stimulate CXCL-mediated innate neutrophilic inflammation that facilitates allergic sensitization and airway inflammation. Myeloid differentiation protein-2 (MD2) is a TLR4 coreceptor, but its role in pollen and cat dander-induced innate and allergic inflammation has not been critically evaluated. Objective To elucidate the role of MD2 in inducing pollen and cat dander-induced innate and allergic airway inflammation. Methods TCMNull (TLR4Null, CD14Null, MD2Null), TLR4Hi, TCMHi cells and human bronchial epithelial cells with siRNA-induced downregulation of MD2 were stimulated with RWPE, other pollen allergic extracts, or cat dander extract (CDE), and activation of NF-κB and/or secretion of the NF-κB-dependent CXCL8 were quantified. Wild type (WT) mice or mice with siRNA knockdown of lung MD2 were challenged intranasally with RWPE or CDE, and innate and allergic inflammation were quantified. Results RWPE stimulated MD2-dependent NF-κB activation and CXCL secretion. Likewise, Bermuda, rye, timothy, pigweed, Russian thistle, cottonwood, walnut and CDE stimulated MD2-dependent CXCL secretion. RWPE and CDE challenge induced MD2-dependent, CD14-independent innate neutrophil recruitment. RWPE induced MD2-dependent allergic sensitization and airway inflammation. Conclusions MD2 plays an important role in induction of allergic sensitization to cat dander and common pollens relevant to human allergic diseases.

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Section: Discussionmentioning

confidence: 99%

“…29 This MD2/TLR4-induced innate neutrophil recruitment facilitates allergic sensitization and allergic airway inflammation. 6, 23 …”

Section: Discussionmentioning

confidence: 99%

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Myeloid differentiation protein 2 facilitates pollen- and cat dander–induced innate and allergic airway inflammation

Hosoki

Boldogh

Aguilera-Aguirre

et al. 2016

Journal of Allergy and Clinical Immunology

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“…Allergic skin inflammation in response to the epicutaneous application of ovalbumin to tapestripped skin is severely impaired in BLT 1 -deficient mice. 117 In mice, the itch-eliciting activity of sphingosylphosphorylcholine is mediated by the direct action of LTB 4 produced by keratinocytes. 118 NC/Nga mice with AD-like skin lesions show a significant increase in LTB 4 levels in the lesional skin; however, topical application of the BLT 1 antagonist, ONO-4057, inhibits spontaneous itch-related behavior.…”

Section: Ltb 4 and Atopic Dermatitismentioning

confidence: 99%

The role of leukotrienes in allergic diseases

Liu

Yokomizo

2015

Allergology International

136

106

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Leukotrienes (LTs), both LTB4 and the cysteinyl LTs (CysLTs) LTC4, LTD4 and LTE4, are implicated in a wide variety of inflammatory disorders. These lipid mediators are generated from arachidonic acid via multistep enzymatic reactions through which arachidonic acid is liberated from membrane phospholipids through the action of phospholipase A2. LTB4 and CysLTs exert their biological effects by binding to cognate receptors, which belong to the G protein-coupled receptor superfamily. LTB4 is widely considered to be a potent chemoattractant for most subsets of leukocytes, whereas CysLTs are potent bronchoconstrictors that have effects on airway remodeling. LTs play a central role in the pathogenesis of asthma and many other inflammatory diseases. This review will provide an update on the synthesis, biological function, and relevance of LTs to the pathobiology of allergic diseases, and examine the current and future therapeutic prospects of LT modifiers.

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“…The expression of eosinophilactive chemokines in the skin is primarily regulated by the T H 2 cytokines IL-4 and IL-13, which are abundantly expressed in the skin after BLT1-mediated T H 2 cell recruitment (34). Additionally, a CCR8+ T H 2 cell subtype enriched in IL-5 is recruited to the skin (48,49).…”

Section: Expression Of Leukotrienes In Inflammatory Skin Diseasesmentioning

confidence: 99%

Leukotrienes orchestrating allergic skin inflammation

Sadik

Sezin

Kim

2013

Experimental Dermatology

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Leukotrienes constitute a group of lipid mediators, which may be subdivided into two groups, with leukotriene B 4 on the one hand and cysteinyl leukotrienes on the other. Although leukotrienes are abundantly expressed in skin affected by diverse chronic inflammatory diseases, including atopic dermatitis, psoriasis, pemphigus vulgaris and bullous pemphigoid, their pathological roles in these diseases have remained elusive. Recent data now reveal that both leukotriene B 4 and cysteinyl leukotrienes are indispensable in the pathogenesis of atopic dermatitis, with leukotriene B 4 initiating the recruitment of inflammatory cells, particularly neutrophils and T H 2 cells into the skin, and cysteinyl leukotrienes later inducing characteristic structural alterations of chronically affected skin, specifically skin fibrosis and keratinocyte proliferation. Thus, these results reveal a sequential cooperation of LTB 4 and cysteinyl leukotrienes to initiate and perpetuate allergic skin inflammation. These new insights highlight leukotrienes as promising therapeutic targets in allergic skin inflammation and should encourage more research into the role of leukotrienes in other inflammatory skin diseases.

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Leukotriene B4-Driven Neutrophil Recruitment to the Skin Is Essential for Allergic Skin Inflammation

Cited by 174 publications

References 37 publications

Myeloid differentiation protein 2 facilitates pollen- and cat dander–induced innate and allergic airway inflammation

Myeloid differentiation protein 2 facilitates pollen- and cat dander–induced innate and allergic airway inflammation

The role of leukotrienes in allergic diseases

Leukotrienes orchestrating allergic skin inflammation

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