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closeReferee Comments: Referee 1 (Mitchell Fink)
Posted by PLOS_ONE_Group on 14 Nov 2007 at 23:37 GMT
Reviewer 1's Review
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1. The authors claim that EGCG blocks LPS-induced HMGB1 release via a mechanism that is not dependent on the "anti-oxidant" properties of EGCG. Data obtained with some other anti-oxidants is cited in support of this statement. But, these other data (not shown by the way) fail to address the issue of whether EGCG-mediated inhibition of HMGB1 release is redox-dependent. Detailed studies, using a wide array of hydrophilic and lipophilic ROS scavengers, would be needed to address this issue. Furthermore, studies designed to determine whether EGCG scavengers ROS in LPS-stimulated macrophages would seem necessary as well. This statement should be softened.
2. The data showing that EGCG inhibits clustering of HMGB1 on macrophages is interesting. But, do these data speak to the issue of inhibition of LPS-induced HMGB1 secretion or inhibiton of the effects on cells of secreted HMGB1? Does EGCG block translocation of HMGB1 from the nucleus to the cytoplasm? Does EGCG block post-translational modification of HMGB1 in LPS-stimulated cells?
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N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.