Toll-like receptor signaling in hen ovarian granulosa cells is dependent on stage of follicle maturation

Woods, Dori C.; Schorey, Jeffrey S.; Johnson, A. L.

doi:10.1530/rep-08-0320

Cited by 57 publications

(31 citation statements)

References 45 publications

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“…Therefore, we developed an in vitro model to investigate the timing of response to LPS on patterns of gene expression in rooster SCs. In hens, it has been reported that the oviduct, as well as ovarian follicular and stromal cells, expresses TLRs, AvBDs, as well as proinflammatory cytokines and chemokines, and the expression of these molecules was upregulated by LPS stimulation (Subedi et al 2007, Abdel Mageed et al 2008, Ozoe et al 2009, Woods et al 2009, Abdelsalam et al 2011, Nii et al 2011. Similar to the female reproductive tract, the gene expression data presented in this study revealed that rooster SCs responded to LPS stimulation.…”

Section: Discussionsupporting

confidence: 59%

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Michailidis¹,

Anastasiadou²,

Guibert³

et al. 2014

Reproduction

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Sertoli cells (SCs) play an important physiological role in the testis, as they support, nourish, and protect the germ cells. As protection of the developing spermatozoa is an emerging aspect of reproductive physiology, this study examined the expression pattern of innate immune-related genes, including avian b-defensins (AvBDs), Toll-like receptors (TLRs), and cytokines, and investigated the time course of an inflammatory response in rooster SCs triggered by exposure to the bacterial endotoxin lipopolysaccharide (LPS). SCs were isolated from 6-week-old chicken, cultured in vitro, and stimulated with 1 mg/ml LPS at different time courses (0, 6, 12, 24, and 48 h). Data on expression analysis revealed that all ten members of the chicken TLR family, nine members of the AvBD family, as well as eight cytokine genes were expressed in SCs. Quantitative real-time PCR analysis revealed that LPS treatment resulted in significant induction of the expression levels of six TLRs, six AvBDs, and four cytokine genes, while two cytokine genes were downregulated and two other genes were unchanged. The increasing interleukin 1b (IL1b) production was confirmed in the conditioned medium. Furthermore, the phagocytosis of SCs was increased after LPS treatment. In conclusion, these findings provide evidence that SCs express innate immunerelated genes and respond directly to bacterial ligands. These genes represent an important component of the immune system, which could be integrated into semen, and present a distinctive constituent of the protective repertoire of the testis against ascending infections.

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Section: Discussionsupporting

confidence: 59%

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Michailidis¹,

Anastasiadou²,

Guibert³

et al. 2014

Reproduction

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“…Intravenous LPS injection may mimic the effects of such bacterial invasion into ovarian tissues. It has been reported that TLR4, which is used to recognize LPS of gram-negative bacteria, is expressed in the granulosa and theca layers (Subedi et al, 2007;Woods et al, 2009). The upregulation of IL-1β, IL-6, and CXCLi2 expression by LPS in the current study could probably be initiated by the interaction of LPS and TLR4 in ovarian tissues.…”

Section: Figurementioning

confidence: 53%

“…Previous reports identified antigen-presenting cells, T and B cells in the follicles that showed unique changes in density affected by age and estrogen (Barua et al, 1998(Barua et al, , 2001; Barua and Yoshimura, 1999). The expression of toll-like receptors, a class of pattern recognition receptors responsible for initiation of the innate immune response, has also been identified in the theca and granulosa layers (Subedi et al, 2007;Woods et al, 2009). Furthermore, the synthesis of avian β-defensins, antimicrobial peptides, in the follicular wall has also been reported (Subedi et al, 2007(Subedi et al, , 2008Abdelsalam et al, 2010;Michailidis et al, 2010).…”

Section: Introductionmentioning

confidence: 94%

Effects of lipopolysaccharide on the expression of proinflammatory cytokines and chemokines and influx of leukocytes in the hen ovary

2011

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The aim of this study was to determine whether the expression of proinflammatory cytokines and chemokines in ovarian cells was changed to recruit heterophils and T cells in response to lipopolysaccharide (LPS), a gram-negative bacterial component. White Leghorn laying hens were intravenously injected with LPS or saline and their ovarian follicles and stroma were collected. Changes in the mRNA expression of IL-1β, IL-6, and CXCLi2 in the theca and granulosa layers and ovarian stroma were analyzed by quantitative reverse transcriptase PCR, whereas proteins of IL-1β and IL-6 were also identified by Western blot analysis. Localization of heterophil-like cells and CD4(+) and CD8(+) T cells was examined by general histology and immunohistochemistry. The expressions of IL-1β, IL-6, and CXCLi2 were significantly increased in the granulosa layer, theca layer, and stroma tissues by 3 to 6 h after LPS injection. Increase of IL-1β and IL-6 proteins in those tissues was also identified 12 h after LPS injection. The LPS stimulation resulted in the increased influx of heterophil-like cells and CD4(+) T cells, but not CD8(+) cells, in the theca layers of follicles. Saline injection affected neither expression of examined proinflammatory cytokines and chemokines nor frequencies of immunocompetent cells. These results suggest that ovarian follicular cells and stromal cells have the ability to express proinflammatory cytokines and chemokines, and their expression is upregulated by LPS in association with the recruitment of heterophil-like cells and T cells. These responses may play roles in local host defense in ovarian follicles.

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“…Activation of TLR signaling occurs following recognition and interaction with conserved small molecular sequences found on the surface of invading pathogens, as well as some endogenous molecules. In animal models of ovarian function, TLRs present on granulosa cells have been implicated in ovulation, a naturally occurring inflammatory-like response [5; 9; 10]. In models of OSE-derived cancer, cancerous human OSE cell lines have also been shown to express multiple TLRs [6; 11].…”

mentioning

confidence: 99%

TLR4 activates NF-κB in human ovarian granulosa tumor cells

Woods¹,

White²,

Dau³

et al. 2011

Biochemical and Biophysical Research Communications

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Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-κB) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to IκB degradation and activation of NF-κB. NF-κB activation was confirmed by nuclear localization of NF-κB p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-κB signaling attenuated LPS-induced TNFαplus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-κB signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-κB does not sensitize GCTs to TRAIL or cisplatin.

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Toll-like receptor signaling in hen ovarian granulosa cells is dependent on stage of follicle maturation

Cited by 57 publications

References 45 publications

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Effects of lipopolysaccharide on the expression of proinflammatory cytokines and chemokines and influx of leukocytes in the hen ovary

TLR4 activates NF-κB in human ovarian granulosa tumor cells

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