Activatory properties of lysophosphatidic acid (LPA) on human THP-1 monocytes

Excessive proliferation as well as the release of proinflammatory mediators from leukocytes represent common phenomena in several important diseases characterized by chronic inflammation such as atherosclerosis, bronchial asthma, and sepsis. In this context, early monocyte proliferation and activation can contribute to the development and progression of inflammatory processes by means of the synthesis and the release of biologically active molecules such as arachidonic acid metabolites, reactive oxygen intermediates (ROI) and nitric oxide (NO). Several evidences identify lysophosphatidic acid (LPA), a small lipid endowed with pleiotropic activities, as an important modulator of both proliferation and activation of different cell types involved in the development of several inflammatory pathologies. However, its exact role on monocyte proinflammatory activation and regulation is not fully understood yet. Aim of the present study was then to investigate possible LPA effects on human monocytic cell line THP-1 activation, evaluated in terms of proliferation, ROI and NO production, and release of arachidonic acid-derived inflammatory mediators, all of them being considered to be key events in leukocytes inflammatory response. Moreover, in order to shed light on complexes and tangled signalling functions of LPA receptors involved in the several biological activities of this lipid, we tried to clarify the contribution of each receptor isoform in mediating LPA effects on THP-1 cells and, particularly, to elucidate LPA signalling transduction pathways leading to proliferation