Impairment of p38 MAPK-mediated cytosolic phospholipase A2 activation in the kidneys is associated with pathogenicity of Candida albicans.
In studying the mechanisms underlying the susceptibility of the kidney to candidal infection, we previously reported that the reduced production of cytokines [i.e. tumour necrosis factor-alpha (TNF-alpha)] via platelet-activating factor (PAF)-induced activation of nuclear factor-kappaB (NF-kappaB) renders the organ susceptible to the fungal burden. In this study, we investigated the possibility that pathogenic Candida albicans may evade clearance and perhaps even multiply by inhibiting elements in the signalling pathway that lead to the production of TNF-alpha. The fungal burden of pathogenic C. albicans in the kidneys was 10(4)-10(5)-fold higher than that of a non-pathogenic strain. PAF-induced early activation of NF-kappaB and TNF-alpha mRNA expression were both observed in the kidneys of mice infected with non-pathogenic strains of C. albicans, but not in mice infected with pathogenic strains. Impairment of PAF-mediated early NF-kappaB activation following infection with pathogenic C. albicans was associated with the prevention of activation of the enzyme cytosolic phospholipase A(2) (cPLA(2)) as well as the upstream pathway of cPLA(2), p38 mitogen-activated protein kinase. Collectively, these findings indicate that C. albicans exerts its pathogenicity through impairing the production of anticandidal cytokines by preventing cPLA(2) activity. This novel mechanism provides insight into understanding pathogenic C. albicans and perhaps identifies a target for its treatment.
Choi
Jung-Hwa
JH
Department of Biological Sciences, College of Natural Sciences, The Institute of Basic Sciences, Chonnam National University, Kwangju, Korea. cjunghwa@hanmail.net
Choi
Eun Kyoung
EK
Park
Sung Jun
SJ
Ko
Hyun-Mi
HM
Kim
Kyoung-Jin
KJ
Han
Su-Ji
SJ
Choi
Il-Whan
IW
Im
Suhn-Young
SY
D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity*; D002177:Candidiasis / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D007674:Kidney Diseases / Q000201:enzymology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010766:Phosphorylation; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014774:Virulence; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D016328:NF-kappa B; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2