Human activity has ‘very likely’ been the primary cause of global warming since the start of the Industrial Revolution (18th–19th century). As a new player in industrial transformation, Malaysia can choose to ignore the warnings of global warming. blame. This may not augur well. Release of greenhouse gases have been categorically linked to climate change and global warming. In her march towards industrialization, Malaysia too has contributed to the release of greenhouse gases. Apart from those arising from natural sources, the industrial sector in Malaysia also releases other types of gases such as the fluorocarbons. This is evident from the worsening air quality in some of our cities. (Copied from article).
Burkholderia pseudomallei, the causative agent of melioidosis, is an intracellular pathogen capable of invading and multiplying in both phagocytic and non-phagocytic cells. Infection results in an inflammatory response involving production of both pro- and anti-inflammatory cytokines. The cellular mechanism regulating this response, believed to play an important role in the pathogenesis of meliodoisis, is not fully understood. In recent years, glycogen synthase kinase-3 (GSK3) has been shown to assume a pivotal role in regulating production of these cytokines. Bacterial infection of host cells activates Toll-like receptors (TLRs) and results in the phosphorylation of GSK3β through activation of the phosphoinositide 3-kinase (PI3K) pathway. In this study, we investigated the effects of GSK3 inhibition in regulating B. pseudomallei-induced inflammatory response in macrophages and A549 epithelial lung cells. Our results showed that infection of cells with B. pseudomallei resulted in the increase of anti-inflammatory cytokine, IL-10 and pro-inflammatory cytokine, TNF-α. Pre-treatment of infected cells with GSK3 inhibitors caused further increase in the level of IL-10 but a significant decrease in TNF-α. These changes corresponded with the detection of phosphorylated GSK3β in infected cells treated with LiCl; suggesting that modulation of inflammatory response in B. pseudomallei infection involves phosphorylation of GSK3β (Ser 9). This could explain our observations from the invasion assays that pre-treatment of B. pseudomallei-infected cells with GSK3 inhibitors resulted in decreased intracellular replication of bacteria within macrophages and A549 epithelial lung cells. In summary, our results demonstrate a regulatory function of GSK3 in the modulation of cytokine levels during B. pseudomallei infection.