MiR-127 Modulates Macrophage Polarization and Promotes Lung Inflammation and Injury by Activating the JNK Pathway

Abstract

A polarized macrophage response is presumed to have a pivotal role in a variety of immunological pathophysiology. However, the molecular mechanism underlying macrophage functional shaping remains largely unknown. In this study, we reveal a pivotal role of miR-127 in macrophage development and thereby the pathogenesis of inflammation and lung injury. In particular, miR-127 was demonstrated to be prominently induced upon TLR engagement and repressed by the M2-prone cytokines. Enforced expression of miR-127 in macrophages resulted in significantly increased production of proinflammatory cytokines, whereas deletion of miR-127 impaired M1 gene expression and led to a M2-biased response. Accordingly, intratracheal administration of miR-127 resulted in an exaggerated pulmonary inflammation and injury. Conversely, antagonizing of miR-127 suppressed production of the proinflammatory cytokines and rendered the mice more refractory to the inflammation-associated pathology. Mechanistically, miR-127 demonstrated to target B cell lymphoma 6 (Bcl6) and remarkably downregulated its expression and subsequently dual specificity phosphatase 1 (Dusp1), which in turn enhanced the activation of JNK kinase and hence the development of proinflammatory macrophages. Thereby, reconstitution with the expression of Bcl6 or Dusp1 or inhibition of JNK activity impaired miR-127–mediated skewing of M1 proinflammatory macrophages, whereas interference of Bcl6 or Dusp1 expression abrogated the anti-inflammatory property of anti–miR-127. Together, these data establish miR-127 as a molecular switch during macrophage development and as a potential target for treatment of inflammatory diseases.

The expression of microRNA-155 and 127 in the neonatal SD rats with acute lung injury induced by lipopolysaccharide

“…The present study indicated that miR-127 was prominently induced in the inflammation-related pulmonary disorders such as LPS, bleomycin, or immunocomplex-induced lung injury and inflammation [22,23], which suggesting a potential role of miR-127 in the inflammatory signaling and lung pathology. Our results showed that the expression of miR-127 in lung tissue BALF were decreased gradually with the increase of dose and the passage of time in the LPS groups.…”

Mitochondria Targeted Peptide Attenuates Mitochondrial Dysfunction, Controls Inflammation and Protects Against Spinal Cord Injury-Induced Lung Injury

“…M1 macrophages are associated with high levels of proinflammatory cytokines and have detrimental effects and toxicity [41]; whereas, M2 macrophages produce anti-inflammatory mediators and exhibit regeneration and protection [40]. The reduction of M1 macrophages alleviates damaging inflammatory activity in the lung [41].…”

Altered microRNA expression profiles in lung damage induced by nanosized SiO2

“…Although individual expression of CTGF in lung tissue induced only mild fibrosis, 33 inhibiting the expression of CTGF can prevent fibrosis formation. 34 microRNA has a lot of different target genes. In the same way, the same target genes often jointly regulated by many different miRNAs.…”