The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization
Abstract
The toll-like receptor (TLR) system is expressed in cumulus cells of ovulated cumulus-oocyte complexes (COCs) and is activated by bacterial lipopolysaccharides (LPS). However, the endogenous ligand(s) for the TLRs and the physiological role(s) in ovulated COCs remain to be defined. Based on reports that hyaluronan fragments can activate TLR2 and TLR4 in macrophages,and that ovulated COCs are characterized by a hyaluronan-rich matrix, we cultured ovulated mouse COCs with purified hyaluronan fragments, treated them with purified hyaluronidase or exposed them to sperm as a physiologically relevant source of hyaluronidase. Hyaluronan fragments or hyaluronidase activated the NFκB pathway and induced Il6, Ccl4 and Ccl5 mRNA expression within 2 hours. Anti-TLR2 and anti-TLR4 neutralizing antibodies significantly suppressed hyaluronan fragment- and hyaluronidase-induced activation of the NFκB pathway and the expression of these genes. When ovulated COCs were cultured with sperm, the expression and secretion of cytokine/chemokine family members were induced in a time-dependent manner that could be blocked by TLR2/TLR4 antibodies or by a hyaluronan-blocking peptide (Pep-1). The chemokines secreted from TLR2/TLR4-stimulated COCs activated cognate chemokine receptors (CCRs)localized on sperm and induced sperm protein tyrosine phosphorylation, which was used as an index of capacitation. Significantly, in vitro fertilization of COC-enclosed oocytes was reduced by the TLR2/TLR4 neutralizing antibodies or by Pep-1. From these results, we propose that TLR2 and TLR4 present on cumulus cells were activated by the co-culture with sperm in a hyaluronan fragment-dependent manner, and that chemokines secreted from COCs induced sperm capacitation and enhanced fertilization, providing evidence for a regulatory loop between sperm and COCs during fertilization.
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Cites
The many roles of chemokines and chemokine receptors in inflammation
Charo, I. F., & Ransohoff, R. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmra052723 · Cited by 2,523
Regulation of lung injury and repair by Toll-like receptors and hyaluronan
Jiang, D., Liang, J., Fan, J., Yu, S., Chen, S., Luo, Y., Prestwich, G. D., Mascarenhas, M. M., Garg, H. G., Quinn, D. A., et al. (2005) · Nature Medicine · doi:10.1038/nm1315 · Cited by 1,401
Oligosaccharides of Hyaluronan Activate Dendritic Cells via Toll-like Receptor 4
Termeer, C., Benedix, F., Sleeman, J., Fieber, C., Voith, U., Ahrens, T., Miyake, K., Freudenberg, M., Galanos, C., & Simon, J. C. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20001858 · Cited by 1,378
Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties
Itano, N., Sawai, T., Yoshida, M., Lenas, P., Yamada, Y., Imagawa, M., Shinomura, T., Hamaguchi, M., Yoshida, Y., Ohnuki, Y., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.35.25085 · Cited by 901
Hyaluronan Fragments Stimulate Endothelial Recognition of Injury through TLR4
Taylor, K. R., Trowbridge, J. M., Rudisill, J. A., Termeer, C. C., Simon, J. C., & Gallo, R. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310859200 · Cited by 545
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Toll-like receptors in neurodegeneration
Okun, E., Griffioen, K. J., Lathia, J. D., Tang, S.-C., Mattson, M. P., & Arumugam, T. V. (2009) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.09.001 · Cited by 429
Jin, M., Fujiwara, E., Kakiuchi, Y., Okabe, M., Satouh, Y., Baba, S. A., Chiba, K., & Hirohashi, N. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018202108 · Cited by 422
DAMPs as mediators of sterile inflammation in aging-related pathologies
Feldman, N., Rotter-Maskowitz, A., & Okun, E. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.01.003 · Cited by 283
Digestion products of the PH20 hyaluronidase inhibit remyelination
Preston, M., Gong, X., Su, W., Matsumoto, S. G., Banine, F., Winkler, C., Foster, S., Xing, R., Struve, J., Dean, J., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23788 · Cited by 107
Yan, K., Zhu, W., Yu, L., Li, N., Zhang, X., Liu, P., Chen, Q., Chen, Y., & Han, D. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.03.027 · Cited by 26
Metadata
- Authors
- Shimada, M., Yanai, Y., Okazaki, T., Noma, N., Kawashima, I., Mori, T., & Richards, J. S.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2008-06-01
- Volume
- 135
- Issue
- 11
- Pages
- 2001-2011
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2140131781
- Cited by
- 187
- References
- 5
- FWCI
- 5.09
- Type
- journal article
- Language
- en
- Open access
- closed
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