FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation

Ge, Xiao Na; Baştan, İdil; Dileepan, Mythili; Greenberg, Yana G.; Ha, Sung Gil; Steen, Kaylee; Bernlohr, David A.; Rao, Savita P.; Sriramarao, P.

doi:10.1152/ajplung.00429.2017

Cited by 37 publications

(32 citation statements)

References 73 publications

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“…Its role in chronic respiratory diseases is poorly understood, although it has been recognized that FABP4 is associated with airway inflammation [19]. Likewise, a dysregulation of airway FABP4 has been previously described in asthma [20] where it has been shown in experimental models that FABP4 participates in the recruitment and activation of eosinophils [21]. In patients with COPD, a dysregulation of systemic FABP4 compared with controls has been suggested [22], which is at variance with our findings here.…”

Section: Previous Studiessupporting

confidence: 55%

Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity

et al. 2020

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Background: For still unclear reasons, chronic airway infection often occurs in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly in those with more severe airflow limitation. Fatty-acid binding protein 4 (FABP4) is an adipokine involved in the innate immune response against infection produced by alveolar macrophages (Mɸ). We hypothesized that airway levels of FABP4 may be altered in COPD patients with chronic airway infection. Methods: In this prospective and controlled study we: (1) compared airway FABP4 levels (ELISA) in induced sputum, bronchoalveolar lavage fluid (BALF) and plasma samples in 52 clinically stable COPD patients (65.2 ± 7.9 years, FEV 1 59 ± 16% predicted) and 29 healthy volunteers (55.0 ± 12.3 years, FEV 1 97 ± 16% predicted); (2) explored their relationship with the presence of bacterial airway infection, defined by the presence of potentially pathogenic bacteria (PPB) at ≥10 3 colony-forming units/ml in BALF; (3) investigated their relationship with the quantity and proportion of Mɸ in BALF (flow cytometry); and, (4) studied their relationship with the severity of airflow limitation (FEV 1 ), GOLD grade and level of symptoms (CAT questionnaire). Results: We found that: (1) airway levels of FABP4 (but not plasma ones) were reduced in COPD patients vs. controls [219.2 (96.0-319.6) vs. 273.4 (203.1-426.7) (pg/ml)/protein, p = 0.03 in BALF]; (2) COPD patients with airway infection had lower sputum FABP4 levels [0.73 (0.35-15.3) vs. 15.6 (2.0-29.4) ng/ml, p = 0.02]; (3) in COPD patients, the number and proportion of Mɸ were positively related with FABP4 levels in BALF; (4) BALF and sputum FABP4 levels were positively related with FEV 1 , negatively with the CAT score, and lowest in GOLD grade D patients. Conclusions: Airway FABP4 levels are reduced in COPD patients, especially in those with airway infection and more severe disease. The relationship observed between Mɸ and airway FABP4 levels supports a role for FABP4 in the pathogenesis of airway infection and disease severity in COPD.

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Section: Previous Studiessupporting

confidence: 55%

Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity

et al. 2020

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“…FABP4 was observed in lung tissue only. Past studies have shown that FABP4 in lungs regulates the eosinophil recruitment and activation [60] , and induces vascular remodeling and angiogenesis in allergic asthma [37] . Our study discovered that the first inflammatory reaction would begin when the allergen enters through the airway with disrupted barrier, where FABP5 is strongly expressed.…”

Section: Discussionmentioning

confidence: 99%

FABP5 as a possible biomarker in atopic march: FABP5-induced Th17 polarization, both in mouse model and human samples

et al. 2020

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Background While the incidence of patients with atopic dermatitis (AD) with atopic march (AM) showing respiratory allergy is steadily rising, the pathomechanism is still unknown. There are currently no biomarkers to predict progression of AM. Methods To explore the mechanism of AM, patients with AD and AM and healthy controls were recruited and RNA microarray, flow cytometry, quantitative real-time polymerase chain reaction, and immunofluorescence staining were performed. We also co-cultured dendritic cells and CD4 + T cells with various Dermatophagoides farinae allergen fractions. Cytokine levels were evaluated using enzyme-linked immunosorbent assay. Findings Both fatty-acid-binding protein 5 (FABP5) and Th17-related genes were more highly expressed in AM. FABP5 knockdown significantly decreased Th17-inducing cytokines in keratinocytes and IL-17A in T cells from AM patients. Further confirmation was obtained using an AM mice model compared to mice without AM. Der f 1, a major D. farinae allergen, increased FABP5 and IL-17A expression in T cells from AM patients. Higher serum FABP5 levels from AM patients were positively correlated with serum IL-17A levels. Interpretation FABP5 expression, possibly enhanced by higher epicutaneous and respiratory sensitization to Der f 1, may directly promote Th17 responses in AD patients with AM. Thus, AM progression can be explained by Th17 reaction induced by FABP5. FABP5 was identified as a potential biomarker in AM. Funding This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT; No. NRF-2017R1A2B4009568), grants of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, and the Republic of Korea (HI13C0010, HI14C1324, HI14C1799).

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“…3 ). FABP4 has been shown to be expressed in lung and bronchoalveolar cells in bronchopulmonary dysplasia 116) , lung lavage cells in sarcoidosis 117) , bronchial epithelial cells 118) and vascular endothelial cells 119) in asthma, eosinophils in allergic airway inflammation 120) , microglia cells in neuroinflammation 121) , resident macrophages/microglial cells and endothelial cells of the hyaloid vasculature in the immature retina of proliferative retinopathy 122) , pulmonary artery endothelial cells in pulmonary thromboembolism 123) , hepatocytes in liver ischemia/reperfusion injury 124) , human placental trophoblasts during placental development 125) , and granulosa cells of the ovary in polycystic ovary syndrome 126, 127) . Furthermore, FABP4 has been detected in human ovarian cancer cells at the adipocyte-tumor cell interface, and FABP4 deficiency in mice substantially impaired metastatic tumor growth 128) .…”

Section: Ectopic Expression Of Fabp4mentioning

confidence: 99%

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases

Furuhashi

2019

J Atheroscler Thromb

197

177

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The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Review Fatty acid-binding proteins (FABPs), a family of lipid chaperones, contribute to systemic metabolic regulation via several lipid signaling pathways. Fatty acid-binding protein 4 (FABP4), known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays important roles in the development of insulin resistance and atherosclerosis in relation to metabolically driven low-grade and chronic inflammation, referred to as 'metaflammation'. FABP4 is secreted from adipocytes in a non-classical pathway associated with lipolysis and acts as an adipokine for the development of insulin resistance and atherosclerosis. Circulating FABP4 levels are associated with several aspects of metabolic syndrome and cardiovascular disease. Ectopic expression and function of FABP4 in cells and tissues are also related to the pathogenesis of several diseases. Pharmacological modification of FABP4 function by specific inhibitors, neutralizing antibodies or antagonists of unidentified receptors would be novel therapeutic strategies for several diseases, including obesity, diabetes mellitus, atherosclerosis and cardiovascular disease. Significant roles of FABP4 as a lipid chaperone in physiological and pathophysiological conditions and the possibility of FABP4 being a therapeutic target for metabolic and cardiovascular diseases are discussed in this review. Fatty Acid-Binding Proteins (FABPs) Fatty acid trafficking in cells affects many aspects of cellular function 3). Fatty acids act both as an energy source and as signals for metabolic regulations including gene expression, inflammatory and metabolic responses, and growth and survival pathways. Fatty acid-binding proteins (FABPs), a family of intracellular lipid chaperones, regulate lipid trafficking and responses in cells and are linked to metabolic and inflammatory pathways 3-6). FABPs are abundantly expressed 14-15-kDa proteins that reversibly bind hydrophobic ligands, such as long-chain fatty acids and other lipids. It has been proposed that FABPs actively facilitate the transport of fatty acids to specific organelles in the cell for lipid oxidation in the mitochondrion or peroxisome, transcriptional regulation in the nucleus, signaling, trafficking and membrane synthesis in the endoplasmic reticulum (ER), and regula-Copyright©2019 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

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FABP4 regulates eosinophil recruitment and activation in allergic airway inflammation

Cited by 37 publications

References 73 publications

Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity

Reduced airway levels of fatty-acid binding protein 4 in COPD: relationship with airway infection and disease severity

FABP5 as a possible biomarker in atopic march: FABP5-induced Th17 polarization, both in mouse model and human samples

Fatty Acid-Binding Protein 4 in Cardiovascular and Metabolic Diseases

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