Cysteinyl Leukotrienes Induce Macrophage Inflammatory Protein-1 in Human Monocytes/Macrophages

Abstract

Background: Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β are known for their chemotactic and proinflammatory effects on monocytes/macrophages which have a cysteinyl leukotriene 1 (CysLT₁) receptor. Methods: We examined MIP-1α and MIP-1β production stimulated by CysLTs (LTC₄, LTD₄, and LTE₄) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs). Moreover, we examined the inhibitory effect of pranlukast, a CysLT₁ receptor antagonist, and inhibitors of three major mitogen-activated protein kinases (MAPK) on the induction of MIP-1α and MIP-1β production by CysLTs. Results: ELISA demonstrated that CysLTs induced MIP-1α and MIP-1β production in THP-1 cells and PBMCs. PCR demonstrated that LTD₄ increased MIP-1α and MIP-1β mRNA expressions in THP-1 cells. Pranlukast blocked MIP-1α and MIP-1β production promoted by LTD₄ in THP-1 cells and PBMCs. Moreover, an inhibitor of extracellular signal-regulated kinase (ERK) attenuated the induction of MIP-1α and MIP-1β production by LTD₄ in THP-1 cells whereas the inhibitors of c-Jun NH2-terminal kinase or p38 MAPK did not. Conclusion: CysLTs induce MIP-1α and MIP-1β production mediated by ERK via binding to the CysLT₁ receptor in human monocytes/macrophages.

An allosteric inhibitor of Mycobacterium tuberculosis ArgJ: Implications to a novel combinatorial therapy

“…This shows that PRK downregulates the 5‐lipoxygenase pathway, thereby reducing the Mtb survival and dissemination within the macrophages. Also, PRK treatment causes a notable decline in the CysLTR1 transcript levels in the macrophages, along with downregulation in the MCP‐1 levels, a downstream effector of CysLTR1 signaling (Ichiyama et al , , ) (Fig G and H). The decrease in the CysLTR1 gene expression could be due to two reasons: (i) since the leukotriene biosynthesis is inhibited, CysLTR1 is downregulated in the absence of its ligand (leukotrienes), (ii) since CysLTR1 levels are upregulated upon Mtb infection, PRK‐mediated reduction in Mtb within macrophages will lead to reduction in the CysLTR1 levels as well.…”

15‐Lipoxygenases regulate the production of chemokines in human lung macrophages

“…PGs E 2 and I 2 , and cysteinyl leukotrienes). In turn, these eicosanoids can modulate chemokine production in monocytes and macrophages (Hashimoto et al ., ; Ichiyama et al ., ; Kuo et al ., ; Buenestado et al ., ; Tsai et al ., ). Furthermore, 15‐HETE can be also produced via COX‐dependent pathways (Levy et al ., ).…”

Human thymic stromal lymphopoietin enhances expression of CD80 in human CD14+ monocytes/macrophages

“…Monocytes/macrophages stimulated with cysteinyl leukotrienes (cysLTs) activated the transcription factor nuclear factor kappa B (NFjB)-and induced monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 [35][36][37]. In addition, cysLTs and TNF-alpha induced matrix metalloproteinase-9 (MMP-9) production in monocyte/ macrophages [38].…”