No abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterised by a dense fibrosing of the lung parenchyma. An association between IPF and cellular senescence is well established and several studies now describe a higher abundance of senescent fibroblasts and epithelial cells in the lungs of IPF patients compared with age-matched controls. The cause of this abnormal accumulation of senescent cells is unknown but evidence suggests that, once established, senescence can be transferred from senescent to non-senescent cells. In this study, we investigated whether senescent human lung fibroblasts (LFs) and alveolar epithelial cells (AECs) could induce a senescent-like phenotype in “naïve” non-senescent LFs in vitro. Primary cultures of LFs from adult control donors (Ctrl-LFs) with a low baseline of senescence were exposed to conditioned medium (CM) from: (i) Ctrl-LFs induced to become senescent using H2O2 or etoposide; (ii) LFs derived from IPF patients (IPF-LFs) with a high baseline of senescence; or (iii) senescence-induced A549 cells, an AEC line. Additionally, ratios of non-senescent Ctrl-LFs and senescence-induced Ctrl-LFs (100:0, 0:100, 50:50, 90:10, 99:1) were co-cultured and their effect on induction of senescence measured. We demonstrated that exposure of naïve non-senescent Ctrl-LFs to CM from senescence-induced Ctrl-LFs and AECs and IPF-LFs increased the markers of senescence including nuclear localisation of phosphorylated-H2A histone family member X (H2AXγ) and expression of p21, IL-6 and IL-8 in Ctrl-LFs. Additionally, co-cultures of non-senescent and senescence-induced Ctrl-LFs induced a senescent-like phenotype in the non-senescent cells. These data suggest that the phenomenon of “senescence-induced senescence” can occur in vitro in primary cultures of human LFs, and provides a possible explanation for the abnormal abundance of senescent cells in the lungs of IPF patients.

Magnaporthe oryzae is a fungal pathogen contributing to rice blast diseases globally via their Avr (avirulence) gene. Although the occurrence of M. oryzae has been reported in Sarawak since several decades ago, however, none has focused specifically on Avr genes, which confer resistance against pathogen associated molecular pattern-triggered immunity (PTI) in host. The objective of this study is to isolate Avr genes from M. oryzae 7’ (a Sarawak isolate) that may contribute to susceptibility of rice towards diseases. In this study, AvrPiz-t, AVR-Pik, Avr-Pi54, and AVR-Pita1 genes were isolated via PCR and cloning approaches. The genes were then compared with set of similar genes from related isolates derived from NCBI. Results revealed that all eight Avr genes (including four other global isolates) shared similar N-myristoylation site and a novel motif. 3D modeling revealed similar β-sandwich structure in AvrPiz-t and AVR-Pik despite sequence dissimilarities. In conclusion, it is confirmed of the presence of these genes in the Sarawak (M. oryzae) isolate. This study implies that Sarawak isolate may confer similar avirulence properties as their counterparts worldwide. Further R/Avr gene-for-gene relationship studies may aid in strategic control of rice blast diseases in future.