Doublecortin-like Kinase 1 highly expressed CD14 monocytes mediates lipopolysaccharide-induced NF-κB activation and acute lung injury

Sepsis is a lethal disease caused by an unbalanced systemic immune response to infection. Acute respiratory distress syndrome (ARDS), a complication of sepsis, is characterized by lung infiltration and lung edema. CD14+ monocytes are the crucial subset of immune cells involved in excessive immune responses of sepsis. Doublecortin-like Kinase 1 (DCLK1) has been reported to be highly expressed in inflammatory diseases. However, its role in immune cell subsets during sepsis remains unclear. Here, we investigated the regulation of DCLK1-expressed CD14+ monocytes in lipopolysaccharide (LPS)-induced acute lung injury and the underlying mechanism of lung inflammation. Mice intraperitoneally injected with LPS exhibited lung inflammation, declined lung function, and increased lung immune cells infiltration. Additionally, the higher expression of myeloperoxidase, VE-cadherin, and iNOS accompanied by DCLK1 induction in LPS-treated murine lung tissues, revealed the potential involvement of DCLK1 in the pulmonary inflammation. The immune profile demonstrated that DCLK1 was highly expressed in CD14+ intrapulmonary immune cells in LPS-induced mice. Moreover, DCLK1 was induced in a time- and dose-dependent manner in LPS-stimulated Raw264.7 cells. The levels of iNOS/NO, IL-6 and TNF-α in LPS-stimulated Raw264.7 were significantly lessened after blocking DCLK1, indicating that DCLK1 regulated NF-κB-mediated inflammation in Raw264.7. Accordingly, DCLK1 highly expressed intrapulmonary CD14+ monocytes may effectively potentiate the induction of NF-κB-mediated pro-inflammatory factors leading to lung inflammation and acute lung injury in endotoxic-induced septic mice.