scholarly journals The Drosophila Inhibitor of Apoptosis Protein DIAP2 Functions in Innate Immunity and Is Essential To Resist Gram-Negative Bacterial Infection

2006 ◽  
Vol 26 (21) ◽  
pp. 7821-7831 ◽  
Author(s):  
François Leulier ◽  
Nouara Lhocine ◽  
Bruno Lemaitre ◽  
Pascal Meier
Keyword(s):  
Immune Response ◽  
Bacterial Infection ◽  
Null Alleles ◽  
Signaling Cascade ◽  
Inhibitor Of Apoptosis ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

ABSTRACT The founding member of the inhibitor of apoptosis protein (IAP) family was originally identified as a cell death inhibitor. However, recent evidence suggests that IAPs are multifunctional signaling devices that influence diverse biological processes. To investigate the in vivo function of Drosophila melanogaster IAP2, we have generated diap2 null alleles. diap2 mutant animals develop normally and are fully viable, suggesting that diap2 is dispensable for proper development. However, these animals were acutely sensitive to infection by gram-negative bacteria. In Drosophila, infection by gram-negative bacteria triggers the innate immune response by activating the immune deficiency (imd) signaling cascade, a NF-κB-dependent pathway that shares striking similarities with the pathway of mammalian tumor necrosis factor receptor 1 (TNFR1). diap2 mutant flies failed to activate NF-κB-mediated expression of antibacterial peptide genes and, consequently, rapidly succumbed to bacterial infection. Our genetic epistasis analysis places diap2 downstream of or in parallel to imd, Dredd, Tak1, and Relish. Therefore, DIAP2 functions in the host immune response to gram-negative bacteria. In contrast, we find that the Drosophila TNFR-associated factor (Traf) family member Traf2 is dispensable in resistance to gram-negative bacterial infection. Taken together, our genetic data identify DIAP2 as an essential component of the Imd signaling cascade, protecting the organism from infiltrating microbes.

Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation

2015 ◽  
Vol 308 (2) ◽  
pp. G92-G99 ◽  
Author(s):  
Jakob Benedict Seidelin ◽  
Sylvester Larsen ◽  
Dorte Linnemann ◽  
Ben Vainer ◽  
Mehmet Coskun ◽  
...  
Keyword(s):  
Wound Healing ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Colon ◽  
Inhibitor Of Apoptosis ◽  
Experimental Ulcer ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

Identification of pathways involved in wound healing is important for understanding the pathogenesis of various intestinal diseases. Cellular inhibitor of apoptosis protein 2 (cIAP2) regulates proliferation and migration in nonepithelial cells and is expressed in human colonocytes. The aim of the study was to investigate the role of cIAP2 for wound healing in the normal human colon. Wound tissue was generated by taking rectosigmoidal biopsies across an experimental ulcer in healthy subjects after 5, 24, and 48 h. In experimental ulcers, the expression of cIAP2 in regenerating intestinal epithelial cells (IECs) was increased at the wound edge after 24 h ( P < 0.05), returned to normal after reepithelialization, and correlated with the inflammatory reaction in the experimental wounds ( P < 0.001). cIAP2 was induced in vitro in regenerating Caco2 IECs after wound infliction ( P < 0.01). Knockdown of cIAP2 caused a substantial impairment of the IEC regeneration through inhibition of migration ( P < 0.005). cIAP2 overexpression lead to formation of migrating IECs and upregulation of expression of RhoA and Rac1 as well as GTP-activation of Rac1. Transforming growth factor-β1 enhanced the expression of cIAP2 but was not upregulated in wounds in vivo and in vitro. NF-κB and MAPK pathways did not affect cIAP2 expression. cIAP2 is in conclusion a regulator of human intestinal wound healing through enhanced migration along with activation of Rac1, and the findings suggest that cIAP2 could be a future therapeutic target to improve intestinal wound healing.

scholarly journals XIAP: a potential determinant of ovarian follicular fate

Reproduction ◽  
2012 ◽  
Vol 144 (2) ◽  
pp. 165-176 ◽  
Author(s):  
Hollian R Phillipps ◽  
Peter R Hurst
Keyword(s):  
Granulosa Cells ◽  
Current Knowledge ◽  
Inhibitor Of Apoptosis ◽  
Caspase Inhibitor ◽  
Follicular Atresia ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Potential Determinant

X-linked inhibitor of apoptosis protein (XIAP), a member of the inhibitor of apoptosis protein family, is involved in regulating a number of functions including receptor-mediated intracellular signalling and early development. Its role as an endogenous caspase inhibitor, however, is the most highly characterised. Consequently, this protein has been implicated as an anti-apoptotic factor in the ovary.In vitroandin vivostudies have begun dissecting the stimuli and signalling networks that lead to XIAP upregulation in granulosa cells. The objective of this review is to briefly summarise the current knowledge concerning XIAP and its interactions with different caspases. Furthermore, XIAP's emerging role in the mammalian ovary will be explored and comparison is made with its functions in the mammary gland. Finally, the idea that XIAP may act as a molecular signalling switch in granulosa cells following detachment from underlying layers to promote follicular atresia will be introduced.

scholarly journals Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and in vivo targeting by SMAC mimetic GDC-0152

2016 ◽  
Vol 7 (8) ◽  
pp. e2325-e2325 ◽  
Author(s):  
A Tchoghandjian ◽  
A Soubéran ◽  
E Tabouret ◽  
C Colin ◽  
E Denicolaï ◽  
...  
Keyword(s):  
Protein Expression ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Smac Mimetic

scholarly journals PtP38 May Increase the Immune Ability of Portunus trituberculatus Stimulated by LPS Imitating a Gram-Negative Bacterial Infection

2021 ◽  
Vol 8 ◽  
Author(s):  
Cheng-Peng Lu ◽  
Chao-Guang Wei ◽  
Jun-Quan Zhu ◽  
Dao-Jun Tang ◽  
Chun-Lin Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Antioxidant Enzymes ◽  
Bacterial Infection ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Portunus Trituberculatus ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Immune Ability ◽  
Immune Related Genes

The P38 mitogen-activated protein kinase (MAPK) signal transduction pathway is widespread in organisms and plays important roles in immune activities. The infection mechanism of environmental gram-negative bacteria on crustaceans is an important scientific problem. In this study, the cDNA full-length sequence of Portunus trituberculatus P38 (PtP38) was cloned and its structure was analyzed by bioinformatics methods. To study the function of the PtP38 gene after a Gram-negative bacterial infection, we injected P. trituberculatus with LPS to activate the immune response instead of directly infecting with Gram-negative bacteria. With LPS stimulation, the expression of the PtP38 gene in different tissues increased significantly. At the same time, the expression of immune-related genes (ALF and crustin) in the hepatopancreas, activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), and inducible nitric oxide synthase (iNOS) enzymes], and expression of apoptosis-related genes (caspase2 and caspase3) were increased significantly. To further conform the function of PtP38 in the immune response, we injected P. trituberculatus with P38 inhibitor and subsequently injected with LPS. The results showed that the expression of immune-related genes was inhibited, the activity of antioxidant enzymes was decreased, and the expression of apoptosis-related genes were inhibited. Thus, we speculated that PtP38 may increase the immune ability by improving the expression of antimicrobial peptides, increasing the activity of oxidative stress-related enzymes, and promoting cell apoptosis in infected P. trituberculatus. This study also laid the foundation for further study of the P38 MAPK signaling pathway and immune mechanism of P. trituberculatus.

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