Circular RNA Targets the /KLF4 Axis to Modulate 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate-Induced Chemokine Transcription in Macrophages.

Exposure to 4,4'-methylene diphenyl diisocyanate (MDI) in the workplace may lead to the development of occupational asthma (OA). However, the specific mechanism(s) by which MDI induces OA are poorly understood. Previous reports have demonstrated that MDI and MDI-glutathione (GSH) conjugate exposure downregulates endogenous human/murine ()-microRNA, resulting in the activation of -regulated signaling pathways in macrophages.

New mechanisms in diisocyanate-mediated allergy/toxicity: are microRNAs in play?

Purpose Of Review: To describe recent findings of diisocyanate-mediated mechanisms in allergy and toxicology by addressing the role of microRNA (miR) in immune responses that may contribute to the development of occupational asthma (OA).

Recent Findings: Studies of diisocyanate asthma have traditionally focused on the immune and inflammatory patterns associated with diisocyanate exposures; however, recognized knowledge gaps exist regarding the detailed molecular mechanism(s) of pathogenesis. Recent studies demonstrate the critical role endogenous microRNAs play as gene regulators in maintaining homeostasis of the human body, and in the pathophysiology of many diseases including asthma.

Human keratinocyte response to 4,4'-methylene diphenyl diisocyanate-glutathione conjugate exposure.

Workplace exposure to diisocyanates like 4,4'-methylene diphenyl diisocyanate can cause occupational asthma (MDI-OA), and the underlying biological pathways are still being researched.Although uncertainty remains, evidence supports the hypothesis that dermal exposure to MDI plays an important role in the development of MDI-OA.Gene expression, proteomics, and informatics tools were utilised to characterise changes in expression of RNA and protein in cultured human HEKa keratinocyte cells following exposure to conjugates of MDI with glutathione (MDI-GSH).

MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4'-methylene diphenyl diisocyanate exposed macrophages.

1. Occupational exposure to 4,4'-methylene diphenyl diisocyanate (MDI) is associated with occupational asthma (OA) development. Alveolar macrophage-induced recruitment of immune cells to the lung microenvironment plays an important role during asthma pathogenesis.

4,4'-Methylene diphenyl diisocyanate exposure induces expression of alternatively activated macrophage-associated markers and chemokines partially through Krüppel-like factor 4 mediated signaling in macrophages.

Occupational exposure to the most widely used monomeric diisocyanate (dNCO), 4,4'-methylene diphenyl diisocyanate (MDI), may lead to the development of occupational asthma (OA). Alveolar macrophages with alternatively activated (M2) phenotype have been implicated in allergic airway responses and the pathogenesis of asthma. Recent studies demonstrate that M2 macrophage-associated markers and chemokines are induced by MDI-exposure, however, the underlying molecular mechanism(s) by which this proceeds is unclear.