Apoptosis related genes expressed in cultured Fallopian tube epithelial cells infected in vitro with Neisseria gonorrhoeae

Abstract

Background: Infection of the Fallopian tubes (FT) by Neisseria gonorrhoeae (Ngo) can lead to acute salpingitis, an inflammatory condition resulting in damage primarily to the ciliated cells, with loss of ciliary activity and sloughing of the cells from the epithelium. Recently, we have shown that Ngo infection induced apoptosis in FT epithelium cells by a TNF-α dependent mechanism that could contribute to the cell and tissue damage observed in gonococcal salpingitis. Aim: To investigate the apoptosis-related genes expressed during apoptosis induction in cultured FT epithelial cells infected in vitro by Ngo. Materials and Methods: In the current study, we used cDNA macroarrays and real time PCR to identify and determine the expression levels of apoptosis related genes during the in vitro gonococci infection of FT epithelial cells. Results: Significant apoptosis was induced following infection with Ngo. Macroarray analysis identified the expression of multiple genes of the TNF receptor family (TNFRSF1B,-4,-6,-10A,-10B and-10D) and the Bcl-2 family (BAK1, BAX, BLK, HRK and MCL-1) without differences between controls and infected cells. This lack of difference was confirmed by RT-PCR of BAX, Bcl-2, TNFRS1A (TNFR-I) and TNFRSF1B (TNFR-II). Conclusion: Several genes related to apoptosis are expressed in primary cultures of epithelial cells of the human Fallopian tube. Infection with Ngo induces apoptosis without changes in the pattern of gene expression of several apoptosis-related genes. Results strongly suggest that Ngo regulates apoptosis in the FT by posttranscriptional mechanisms that need to be further addressed.

Tumour necrosis factor-α is the signal induced by mating to shutdown a 2-methoxyestradiol nongenomic action necessary to accelerate oviductal egg transport in the rat

“…In contrast to other species (Hunt et al 1993, Srivastava et al 1996, Wijayagunawardane et al 2003, Reyes et al 2007), we did not find expression of TNF-a mRNA in the endosalpinx and myosalpinx of the rat oviduct, indicating that the regulation of the transcription of the TNF-a mRNA in the mammalian oviduct could be species specific. However, the number of species studied in this regard is too small to formulate a phylogenetic based algorithm describing species specificity in the presence of the transcript for TNF-a in the mammalian oviduct.…”

“…Tumour necrosis factor-a (TNF-a) is a cytokine associated with immune responses in the female genital tract (Tremellen et al 1998, Maisey et al 2003, Morales et al 2006. Furthermore, transcripts of TNF-a and their receptors are expressed in mice, bovine and human oviduct (Hunt et al 1993, Srivastava et al 1996, Wijayagunawardane et al 2003, Reyes et al 2007. Moreover, there are data showing that TNF-a could participate in reproductive functions including fertilization, embryo development and implantation (Rasmussen et al 1999, Lee et al 2000, Torchinsky et al 2003, Abdo et al 2008, Choo et al 2011.…”

IL-17C is a driver of damaging inflammation duringNeisseria gonorrhoeaeinfection of human Fallopian tube

“…This hypothesis is supported by studies from multiple groups showing that anti-apoptotic factors including BCL2A1 (Bfl-1), BIRC3 (c-IAP-2), and PTGS2 (Cox-2) are upregulated upon gonococcal infection of epithelial monolayers lacking ciliated cells(94, 95). Studies of non-ciliated (secretory) Fallopian tube epithelial cells show that gonococcal infection does not induce pro-apoptosis transcripts TNFRSF1B, TNFRSF1A, TNFRSF4, TNFRSF6, TNFRSF10A, TNFRSF10B, TNFRSF10D, BAK1, BAX, BLK, HRK , or MCL1 but does induce pro-apoptotic caspase 3(96, 97). Curiously, induction of caspase 3 is only observed at a low multiplicity of infection (MOI).…”

Tissue Models for Neisseria gonorrhoeae Research—From 2D to 3D

“…Primary cells derived from different parts of the female reproductive tract were also used in various studies. Among them are those of cervix (Edwards et al, 2000;Swanson et al, 2001;Edwards et al, 2002;Steichen et al, 2008;Edwards, 2010;Jennings et al, 2011), endometrium (Christodoulides et al, 2000;Timmerman et al, 2005), and fallopian tube (Swanson et al, 2001;Maisey et al, 2003;Morales et al, 2006;Reyes et al, 2007). Additionally, immortalized human cervical epithelial cells were introduced in 2009 and used in studies of gonococcal biofilm formation (Falsetta et al, 2009) as well as studies of N. gonorrhoeae interaction with cell surface glycans (Semchenko et al, 2019).…”

“…molecules, whereas primary cervical cells, but also ME180 cell line, did (Swanson et al, 2001). Primary cells are also a model of choice when various signaling or cell death pathways are investigated or in gene expression studies (Reyes et al, 2007), because tumor cell lines might be too divergent from the original tissues for these purposes. From the technical view, the fact that most primary cells can be passaged for only a few passages represents a significant drawback.…”