Suppression of edr2-mediated powdery mildew resistance, cell death and ethylene-induced senescence by mutations in ALD1 in Arabidopsis

EDR2 is a negative regulator of the defense response and cell death in Arabidopsis.Loss-of-function of EDR2 leads to enhanced resistance to powdery mildew.To identify new components in the EDR2 signal transduction pathway,mutations that suppress edr2 resistant phenotypes were screened.Three mutants,edts5-1,edts5-2 and edts5-3（edr two suppressor 5）,were identified.The EDTS5 gene was identified by map-based cloning and previously was shown to encode an aminotransferase（ALD1）.Therefore we renamed these three alleles ald1-10,ald1-11 and ald1-12,respectively.Mutations in ALD1 suppressed all edr2-mediated phenotypes,including powdery mildew resistance,programmed cell death and ethylene-induced senescence.Accumulation of hydrogen peroxide in edr2 was also suppressed by ald1 mutation.The expression of defense-related genes was up-regulated in the edr2 mutant,and the up-regulation of those genes in edr2 was suppressed in the edr2/ald1 double mutant.The ald1 single mutant displayed delayed ethylene-induced senescence.In addition,ald1 mutation suppressed edr1-mediated powdery mildew resistance,but could not suppress the edr11edr2 double-mutant phenotype.These data demonstrate that ALD1 plays important roles in edr2-mediated defense responses and senescence,and revealed a crosstalk between ethylene and salicylic acid signaling mediated by ALD1 and EDR2.

Cytokines and fatty liver diseases

Cytokines are considered crucial players in inflammatory-associated disorders throughout the body.Fatty liver diseases such as alcoholic liver disease(ALD)and non-alcoholic fatty liver disease(NAFLD)are commonly characterized by lipid accumulation and in a substantial subset of patients with inflammation in the liver.Amount of inflammation affects long-term outcome of liver disease including evolution of liver fibrosis,cirrhosis and hepatocellular carcinoma.Especially the pro-inflammatory cytokines Interleukin(IL)-1(αandβ)and tumor necrosis factor(TNF)αplay a central role in many stages of liver diseases mediating fundamental aspects of those diseases including acute phase protein synthesis,lipid metabolism,cholestasis and degree of fibrosis.These key cytokines released mainly by mononuclear cells affect all liver cell types and orchestrate the production of many other mediators relevant in chronic liver diseases.Inflammatory cytokines also regulate crucially the development of insulin resistance,a key component of NAFLD.Blocking these critical mediators of inflammation by specific antibodies,especially TNFα,has so far not been proven successful in alcoholic steatohepatitis,a cytokine-driven disorder.In summary,inflammatory cytokines are continuously present locally and systemically in patients with advanced fatty liver diseases,mediating and affecting the clinical phenotype and many features of these disorders.