Proteoglycan digesting enzymes that are present during inflammation further modulate the characteristics of the layer. Taken together, this makes it problematic to evaluate the significance of the IL-8-GAG-interaction in vivo. In vitro experiments revealed www.selleckchem.com/products/PF-2341066.html the importance of 6-O-sulfation for binding of IL-8 to GAGs. However, it remains unknown which particular patterns of sulfation and dynamic alterations in these patterns contribute to the regulation of IL-8 functions in vivo. The creation of artificially modified matrices is a fundamental tool in regenerative medicine to improve wound healing and immunological safety of graft materials. Thus, it is highly important to know how these materials interact with cytokines and immune cells.
As shown on selected examples, the introduction of sulfate groups into a hyaluronan matrix significantly improves its binding of IL-8. Thus, in immune responses IL-8 is a necessary component to direct immune cells to infected/injured sites. Hence, it is a high challenge to gain insight into further unknown details of functional and regulatory aspects of this chemokine. Acknowledgments This work was supported by the German Research Foundation (SFB-TRR67, A6, B3) and the German Federal Ministry of Education and Research (BMBF, PtJ-Bio, 0315883). Glossary Abbreviations: DARC duffy antigen receptor for chemokines GAGs glycosaminoglycans Gal D-galactose GalNAc N-acetyl-D-galactosamine GlcA D-glucuronic acid GlcNAc N-acetyl-D-glucosamine IdoA L-iduronic acid IL-8 interleukin-8 PMNs polymorphonuclear leukocytes ROS reactive oxygen species Footnotes Previously published online: www.
landesbioscience.com/journals/biomatter/article/21316
The extracellular matrix (ECM) is a complex tissue component that is omnipresent in all vertebrates. The replacement or reconstruction of damaged ECM is the major subject of regenerative medicine and particularly important in industrialized countries where the population enjoys a high life expectation which, however, also leads to an over-aged population. Therefore, the interest in ECM is not stemming from the ECM itself but much more from its role in medicine. Although ECM is found in almost all parts of the human body, we will focus here on bone, cartilage, and skin because these tissues are (1) in the focus of our current research interest and (2) of significant medical relevance.
1 Regenerative medicine2 is a rapidly developing discipline of medical sciences and aims��in addition to the repair of more complex organs (such as liver)��particularly at the ECM. This field is particularly important as ECM-related diseases are of tremendous socioeconomic significance: for instance, about 46.4 million Drug_discovery US citizens (approximately 21% of the overall population) are currently suffering from any form of arthritic diseases.3 Logically, the related social consequences (e.g., early retirement and loss of life quality) and costs for the health care system are immense.