Basic—Alimentary TractRegulation of Colonic Epithelial Repair in Mice by Toll-Like Receptors and Hyaluronic Acid
Section snippets
Chemicals and Reagents
DSS was purchased from TdB Consultancy AB (Uppsala, Sweden). This product was tested for endotoxin by Associates of Cape Cod, Inc (East Falmouth, MA); it was found to be endotoxin free. HA (mol wt, 750 kilodaltons) was from Sigma (St. Louis, MO). High-molecular-weight HA (Healon; mol wt, 2 × 103 kilodaltons) was from Physician Sales and Services (St. Louis, MO). PEP-1 (GAHWQFNALTVR) and scrambled control peptide (WRHGEALTAVNQ) were from Sigma-Genosys (St. Louis, MO).20
Animals
Adult (6–8 weeks old)
DSS Induces the Expression of HAS-2 and HAS-3 and the Synthesis of HA in a MyD88-Dependent Manner
In the normal mouse colon, HA is distributed in the lamina propria (Figure 1A). After treatment with DSS, there was a progressive increase in HA in the lamina propria of wild-type (WT) mice. The increased HA expression is extracellular and located between the crypts. At baseline, the distribution of HA in the colons of MyD88−/− mice was similar to that seen in WT mice; however, there was no increase in HA expression with DSS treatment in MyD88−/− mice. DSS induced an increase in plasma HA level
Discussion
DSS-induced colitis is more severe in mice deficient in TLR4 or MyD88, a TLR adaptor molecule; this suggests that TLR4 plays an important role in the host defense response to DSS-induced colitis.17, 18, 19 It has been assumed that LPS is the TLR ligand that mediates the host defense response in DSS-induced colitis. However, HA also binds to TLR4, and HA binding to TLR4 promotes the protective component of the host response in sterile skin and lung injury models where LPS is not involved.13, 14
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by National Institutes of Health grants R01DK33165 and R01DK55753.