Macrophages—common culprit in obesity and asthma

Abstract

Macrophages are essential innate immune cells that also regulate local metabolism.Endogenous or exogenous stimuli may polarize macrophages toward phenotypes that serve distinct innate immunological metabolic functions. IFN-c or lipopolysaccharide (LPS) polarizes macrophages toward the M1, or "classically activated" phenotype that participates in defense against intracellular pathogens. IL-4, IL-13, or chitin polarizes macrophages toward the M2, or "alternatively activated" phenotype, which defends against multicellular nematodes and fungi. As macrophages polarize in local environments, M1 and M2 macrophages may coexist in different organs and may differentially affect asthma and obesity, two comorbid diseases where polarized macrophages contribute to their pathogenesis. While M1 macrophages are considered beneficial in asthma and contribute to the pathology of obesity, M2 macrophages contribute to the pathology of asthma, but limit metabolic syndrome associated with obesity. Here, we discuss the roles for M1 and M2 macrophages in asthma and obesity, and propose a model by which M1-mediated inflammation in adipose tissue enhances M2-mediated inflammation in the asthmatic lung. Metabolic syndrome is considered a state of chronic inflammation that is characterized by the production of cytokines (eg, TNF-a, IL-6, and IL-1b) and acute phase reactants (eg, C-reactive protein and plasma plasminogen inhibitor-1 (PAI-1) and activation of an inflammatory signaling network).1 Asthma is also a common chronic inflammatory disease. According to WHO, 235 million people currently suffer from asthma and asthma is the most common noncommunicable disease among children (http://www.who.int/mediacentre/factsheets/fs307/en/). Obesity and asthma are often coassociated. The prevalence of asthma in obese subjects is about twofold higher than in lean subjects, and these two comorbid diseases appear to affect each other's severity.For example, the severity of asthma increases with increasing BMI, 2 and surgical procedures that induce weight loss alleviate asthma symptoms.3 In addition, asthmatics with BMIs greater than 25 kg/m 2 are more likely to be resistant to pharmacologic therapy, to require more hospitalizations, and to report a lower quality of life. 3,4 Similarly, metabolic syndrome is more refractory in adolescent obese males with mild persistent asthma than in nonasthmatic obese --

HDAC inhibitor sodium butyrate prevents allergic rhinitis and alters lncRNA and mRNA expression profiles in the nasal mucosa of mice

“…The regulation of the immune system in early life by the microbiota may be associated with allergy development (52). The pathology of bronchial asthma demonstrates a multicellular process (53). AR rats exhibit microvascular remodeling of the nasal mucosa (54).…”

The Caspase Inhibitor Z-VAD-FMK Alleviates Endotoxic Shock via Inducing Macrophages Necroptosis and Promoting MDSCs-Mediated Inhibition of Macrophages Activation

“…In the early stages of endotoxin shock, hyper-activated macrophages can drive tissue damage by producing excessive amounts of pro-inflammatory cytokines. After stimulation with bacterial lipopolysaccharide (LPS), macrophages can differentiate into classically macrophages (M1) that can secrete pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-12, and produce nitric oxide (NO) (6)(7)(8)(9)(10)(11). In the early stages of endotoxin shock, LPS can bind TLR4 and trigger MyD88-and TRIF-dependent expression of pro-inflammatory cytokines and type I interferons (12)(13)(14).…”

Airway Epithelial Dynamics in Allergy and Related Chronic Inflammatory Airway Diseases

“…M2 macrophages are induced by IL-4 and IL-13, and are involved in wound healing and anti-inflammatory responses (Sica and Mantovani, 2012;Liu et al, 2013;Shapouri-Moghaddam et al, 2018). It is possible that M1-mediated inflammation in the adipose tissue of obese patients enhances M2-mediated asthmatic inflammation of the lungs (Sharma et al, 2017). CD163 is a known marker for M2 macrophages, it seems to have a role in airway hyperresponsiveness and asthma (Jiang and Zhu, 2016;Tokunaga et al, 2019).…”