Tranglutaminase 2 contributes to the asthmatic inflammation by modulating activation of alveolar macrophages

Abstract

Background Transglutaminase 2 (TG2), a multifunctional calcium‐dependent acyltransferase, is upregulated in asthmatic airways and reported to play a role in the pathogenesis of allergic asthma. However, the underlying mechanism is not fully understood. Objective To investigate the role of TG2 in alternative activation of alveolar macrophages by using murine asthma model. Methods TG2 expression was assessed in induced sputum of 21 asthma patients and 19 healthy controls, and lung tissue of ovalbumin (OVA)‐induced murine asthma model. To evaluate the role of TG2 in asthma, we developed an OVA asthma model in both TG2 null and wild‐type mice. The expression of M2 macrophage markers was measured by fluorescence‐activated cell sorting (FACS) after OVA sensitization and challenge. To evaluate the effect of TG2 inhibition in vitro, interleukin 4 (IL‐4) or IL‐13‐stimulated expression of M2 macrophage markers was measured in CRL‐2456 cells in the presence and absence of a TG2 inhibitor. Results The expression of both TG2 and M2 markers was increased in the sputum of asthmatics compared with that of healthy controls. The expression of TG2 was increased in macrophages of OVA mice. Airway hyperresponsiveness, and the number of inflammatory cells, including eosinophils, was significantly reduced in TG2 null mice compared with wild‐type mice. Enhanced expression of M2 markers in OVA mice was normalized by TG2 knockout. IL‐4 or IL‐13‐stimulated expression of M2 markers in alveolar macrophages was also attenuated by TG2 inhibitor treatment in vitro. Conclusion Our results suggest that TG2‐mediated modulation of alveolar macrophage polarization plays important roles in the pathogenesis of asthma.

Osthole regulates N6‐methyladenosine‐modified TGM2 to inhibit the progression of rheumatoid arthritis and associated interstitial lung disease

“…Moreover, the in vitro studies also verified that OS suppressed the proliferation and polarization of CD11b + M2 macrophages by reducing TGM2 expression. Previous studies also demonstrated that TGM2 mediated the polarization of M2 macrophage and cell proliferation, 17,52 further supporting the findings obtained in our investigation. Interestingly, the reduced number of infiltrated M2 macrophages and inhibited M2 polarization might contribute to the suppression of RA‐ILD 53 .…”

Immunopharmacological Activities of Luteolin in Chronic Diseases

“…Asthma is worsened by inflammation, which also causes the release of Th2 cytokines, including IL-4 and IL-13, that subsequently stimulate the development of M2 macrophage markers [40,41]. Many M1 macrophages are found in asthma patients, and reducing M1 macrophages and increasing M2 macrophages is one way to treat asthma [42]. In 2022, Gong et al demonstrated that luteolin increased M2 polarization and decreased M1 polarization in macrophages that had been stimulated by THP-1.…”

Isoalantolactone alleviates ovalbumin‑induced asthmatic inflammation by reducing alternatively activated macrophage and STAT6/PPAR‑γ/KLF4 signals

“…Asthma is generally associated with enhanced type 2 immune responses, including increased production of IL-4, IL-5, IL-13, CCL17 and CCL22 (23)(24)(25). Therefore, the generation of IL-4, IL-5, IL-13, CCL17 and CCL22 in BALF was detected.…”

“…IAL inhibits alternatively activated macrophages in vitro. it is well established that alternatively activated M2 macrophages, induced by IL-4, serve an important role in asthmatic inflammation (24). Arg-1 and Ym-1 are expressed by alternatively activated macrophages during asthmatic inflammation (26) and ccl17 and ccl22 are the main chemokines involved in eosinophil recruitment (7).…”