House Dust Mite Allergen Regulates Constitutive Apoptosis of Normal and Asthmatic Neutrophils via Toll-Like Receptor 4

• Published in: PloS one Vol. 10; no. 5; p. e0125983
• Main Authors: Kim, Do Hyung, Choi, Eugene, Lee, Ji-Sook, Lee, Na Rae, Baek, Seung Yeop, Gu, Ayoung, Kim, Da Hye, Kim, In Sik
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.05.2015; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Adolescent; Adult; Aged; Aged, 80 and over; Airway management; AKT protein; Allergens; Allergens - pharmacology; Allergic diseases; Allergies; Alveoli; Animals; Apoptosis; Apoptosis - drug effects; Asthma; Asthma - genetics; Asthma - immunology; Asthma - pathology; Bronchoalveolar lavage; Bronchoalveolar Lavage Fluid - cytology; Bronchus; Calgranulin A - genetics; Calgranulin A - immunology; Calgranulin B - genetics; Calgranulin B - immunology; Care and treatment; Case-Control Studies; Cell Extracts - pharmacology; Dermatophagoides farinae - chemistry; Dermatophagoides farinae - immunology; Dermatophagoides pteronyssinus - chemistry; Dermatophagoides pteronyssinus - immunology; Development and progression; Dust; Extracellular signal-regulated kinase; Female; Gene Expression Regulation; Health aspects; House dust; Humans; Immune system; Immunity; Immunoglobulins; Inflammation; Inhibition; Innate immunity; Kinases; Laboratories; Leukocytes (neutrophilic); Male; Mcl-1 protein; Medicine; Middle Aged; Mites; Mitogen-Activated Protein Kinase 1 - genetics; Mitogen-Activated Protein Kinase 1 - immunology; Mitogen-Activated Protein Kinase 3 - genetics; Mitogen-Activated Protein Kinase 3 - immunology; Neutrophils; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - pathology; NF-kappa B - genetics; NF-kappa B - immunology; NF-κB protein; Pathogenesis; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - immunology; Primary Cell Culture; Proteins; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - immunology; Review boards; Risk factors; Science; Signal Transduction; Signaling; src-Family Kinases - genetics; src-Family Kinases - immunology; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Toll-like receptors; Trends; Tumor necrosis factor-TNF; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125983

House dust mites (HDMs) induce allergic diseases such as asthma. Neutrophil apoptosis is an important process of innate immunity, and its dysregulation is associated with asthma. In this study, we examined the effects of HDM on constitutive apoptosis of normal and asthmatic neutrophils. Extract of Dermatophagoides pteronissinus (DP) inhibited neutrophil apoptosis, but Dermatophagoides farinae extract had no effect. Anti-apoptotic signaling mediated by DP involves in TLR4, Lyn, PI3K, Akt, ERK, and NF-κB in normal neutrophils. DP delayed cleavage of procaspase 9 and procaspase 3 and the decrease in Mcl-1 expression. Supernatant collected from DP-treated normal neutrophils inhibited the constitutive apoptosis of normal neutrophils, and S100A8 and S100A9 were identified as anti-apoptotic proteins in the supernatant. S100A8 and S100A9 transduced the anti-apoptotic signal via TLR4, Lyn, PI3K, Akt, ERK, and NF-κB. DP also suppressed asthmatic neutrophil apoptosis and induced secretion of S100A8 and S100A9, which delayed the constitutive apoptosis. The anti-apoptotic effects of DP, S100A8 and S100A9 in asthmatic neutrophils are associated with TLR4, Lyn, PI3K, Akt, ERK, and NF-κB. The concentrations of S100A8 and S100A9 were significantly elevated in asthmatic bronchoalveolar lavage fluid (BALF) when compared to normal BALF (p<0.01), but not in serum. S100A8 concentration in BALF was positively correlated with the number of BALF neutrophils and negatively correlated with FEV1(%). These findings improve our understanding of the role of HDM in regulation of neutrophil apoptosis in normal individuals and asthmatics and will enable elucidation of asthma pathogenesis.