Aquaporins in Immune Cells and Inflammation: New Targets for Drug Development

Abstract

The mammalian immune system senses foreign antigens by mechanisms that involve the interplay of various kinds of immune cells, culminating in inflammation resolution and tissue clearance. The ability of the immune cells to communicate (via chemokines) and to shift shape for migration, phagocytosis or antigen uptake is mainly supported by critical proteins such as aquaporins (AQPs) that regulate water fluid homeostasis and volume changes. AQPs are protein channels that facilitate water and small uncharged molecules’ (such as glycerol or hydrogen peroxide) diffusion through membranes. A number of AQP isoforms were found upregulated in inflammatory conditions and are considered essential for the migration and survival of immune cells. The present review updates information on AQPs’ involvement in immunity and inflammatory processes, highlighting their role as crucial players and promising targets for drug discovery.

Recent Update on the Molecular Mechanisms of Gonadal Steroids Action in Adipose Tissue

“…Since AQPs have been recognized as functionally involved in immune cell activity such as priming and inflammasome activation, transendothelial migration and phagocytosis, development of AQP-oriented drugs gives a promising opportunity in future therapies against metabolic diseases [ 203 ]. Up to date, several AQP modulators have been proposed and even patented for use for diagnostic and therapeutic purposes [ 295 , 296 ].…”

“…Among the most promising AQP modulators, which are relatively safe and able to effectively prevent inflammation, are the gold(III) bipyridyl compound Auphen and compounds DFP00173, Z433927330 and HTS13286. The physiological effects of their administration are summarized in [ 203 ]. An alternative AQPs-targeted approach can be based on modulation of aquaporins at the post-transcriptional level.…”

“…It is also worth mentioning that peroxiporins are especially important in functioning of the immune system [ 203 ]. Due to their ability to facilitate hydrogen peroxide fluxes across biological membranes, they are tightly involved in redox balance and modulation of oxidative stress [ 186 ] and were reported to regulate immunological processes including inflammasome priming and activation [ 204 ].…”

“…Moreover, the water transport via aquaporins in immune cells enables them for shape and volume changes as well as maintaining an appropriate osmotic gradient across cell membrane, which are critical factors in cell-to-cell communication (via chemokines) and induction of changes in shape for migration, phagocytosis or antigen uptake [ 203 ]. Thus, aquaporins provide also a direct hydromechanical support for immune cells which is essential for their proper functioning.…”

Organ Specific Differences in Alteration of Aquaporin Expression in Rats Treated with Sennoside A, Senna Anthraquinones and Rhubarb Anthraquinones

“…Recently, it has been suggested that AQPs are involved in the development of inflammatory mechanisms, supported by the detection of several isoforms in cells of both the innate and adaptive immune system and the demonstration of their dysregulation in various human diseases. For example, AQP8 downregulation was described in human Crohn’s disease and ulcerative colitis biopsies [ 38 ]. Our study showed that drug induced Aqp8 downregulation occurred in a dose dependent manner, which could lead to colon inflammation after long-term usage.…”