Asthma and lower airway diseaseRole of C/EBP homologous protein and endoplasmic reticulum stress in asthma exacerbation by regulating the IL-4/signal transducer and activator of transcription 6/transcription factor EC/IL-4 receptor α positive feedback loop in M2 macrophages
Section snippets
Methods
Further details can be found in the Methods section in this article's Online Repository at www.jacionline.org.
Asthmatic patients and mice exhibit aberrant Chop expression and ER stress
We first examined the expression of CHOP in induced sputum samples obtained from asthmatic patients. CHOP was expressed at low levels in sputum derived from control subjects, whereas higher levels of CHOP were detected in induced sputum samples originating from asthmatic patients (Fig 1, A). We also examined the expression of binding immunoglobulin protein (BIP), another marker of ER stress. Similar to CHOP, BIP was expressed at significantly higher levels in asthmatic patients compared with
Discussion
In the present study we demonstrated that asthmatic patients and mice with OVA-induced allergic airway inflammation exhibit aberrant CHOP expression along with ER stress. Interestingly, CHOP was overexpressed in macrophages in both asthmatic patients and mice with OVA-induced allergic airway inflammation. Accordingly, Chop deficiency provided protection for mice against airway inflammation, remodeling, and AHR after repeated OVA challenges. Specifically, the loss of Chop protected mice from
References (27)
Selecting the correct treatment for asthma adherence studies
J Allergy Clin Immunol
(2016)- et al.
Cytokines in symptomatic asthma airways
J Allergy Clin Immunol
(1992) - et al.
Alternatively activated macrophages and airway disease
Chest
(2011) - et al.
More alternative activation of macrophages in lungs of asthmatic patients
J Allergy Clin Immunol
(2011) - et al.
Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore-induced allergic airway disease
J Allergy Clin Immunol
(2010) - et al.
Phenotypic characterization of lung macrophages in asthmatic patients: overexpression of CCL17
J Allergy Clin Immunol
(2012) - et al.
Therapeutic response to HMGB1-R3V6-conjugated Ym1/Ym2 siRNA complex in ovalbumin-induced murine asthma
J Control Release
(2015) - et al.
Endoplasmic reticulum stress and the related signaling networks in severe asthma
Allergy Asthma Immunol Res
(2015) - et al.
Endoplasmic reticulum stress controls M2 macrophage differentiation and foam cell formation
J Biol Chem
(2012) - et al.
Chop deficiency protects mice against bleomycin-induced pulmonary fibrosis by attenuating M2 macrophage production
Mol Ther
(2016)
Inhaled long-acting beta2 agonists enhance glucocorticoid receptor nuclear translocation and efficacy in sputum macrophages in COPD
J Allergy Clin Immunol
IL-17-producing alveolar macrophages mediate allergic lung inflammation related to asthma
J Immunol
Attenuation of the programmed cell death-1 pathway increases the M1 polarization of macrophages induced by zymosan
Cell Death Dis
Cited by (69)
DDIT3 aggravates pulpitis by modulating M1 polarization through EGR1 in macrophages
2023, International ImmunopharmacologyP311 Promotes IL-4 Receptor‒Mediated M2 Polarization of Macrophages to Enhance Angiogenesis for Efficient Skin Wound Healing
2023, Journal of Investigative DermatologyCitation Excerpt :In the process of skin wound healing, M2 macrophages secrete many cytokines such as TGF-β, IL-10, and VEGF in wound healing, which can inhibit local inflammation and promote granulation tissue formation by enhancing angiogenesis and fibrosis (Hesketh et al., 2017). Previous studies have shown that the intrinsic angiogenesis and fibrosis-promoting ability of P311−/− vascular endothelial cells per se is weakened (Tan et al., 2010; Wang et al., 2017; Zhou et al., 2020). However, the regulation of P311−/− M2 macrophages on angiogenesis and fibrosis skin wound healing remains unknown.
Clevudine attenuates bleomycin-induced early pulmonary fibrosis via regulating M2 macrophage polarization
2021, International Immunopharmacology
Disclosure of potential conflict of interest: All of the authors declare that their institutions received the National Natural Science Foundation of China (81130014, 81530024, 81428001, 81470226, and 81570024), the Program Project for Chronic Diseases from the Ministry of Science and Technology (2016YFC1305002), the Funding for Generation of Experimental Animals from the Hubei State Technology Department (2015BCE100), the Program for Changjiang Scholars and Innovative Research Team in University (IRT_14R20), and the Multi-interdisciplinary Creative Team for Diabetes Research (2017-4) from Tongji Medical College, Huazhong University of Science & Technology.
- ∗
These authors contributed equally to this work.