A potassium ion channel is involved in cytokine production by activated human macrophages

Macrophages play an important role in immune and inflammatory responses, largely through secretion of bioactive molecule such as cytokines. While calcium is known to be an important regulator of this process, less is known about the role of other ions and the ion channels that regulate them. We have previously implicated an outwardly rectifying potassium channel (Kor) in this process and for this reason we have investigated the role of potassium (K+) and K+ channels in the regulation of tumour necrosis factor-alpha (TNF-alpha)and interleukin (IL)-8 production by activated human culture-derived macrophages. The effect of blockade of Kor is to inhibit phorbol myristate acetate (PMA)-induced cytokine production by translational or post-translational mechanisms, an effect that is duplicated by increasing extracellular K+. By contrast, the effects of K+ on LPS-stimulated cells are far more complex and are probably mediated through the change of osmolality and occur largely at the mRNA level. This data directly implicates K+, and its regulation through Kor, in early events following PMA stimulation of these cells.