The Mechanism Causing CCL3&CXCL14Concentration Changes In Bone Marrow Microenvironment After Irradiation Injury

Background: Irradiation commonly causes different changes on geneexpression that lead to a series of pathological and physiological changes.The study of the injury and recovery mechanism causing these differencescan provide references for radiation protection and development of drugs.After the identification of differently expressed genes in our previous study,we identified that immunity response including hematopoiesis is the keyprocess that helps organism recover from irradiation injury by improvinghematopoietic stem cells (HSCs) self-renewal, proliferation anddifferentiation. In our study, we explored the mechanism of chemokineCCL3and CXCL14that participate in immunity process during IR recoveryphase. We developed the hypothesis that the suppression of HSCproliferation was decreased after IR injury through two pathways at least:downregulation of CCL3secretion spontaneously and increasing CCL3proteolysis and CXCL14protein concentration was up-regulated that meansCXCL14might promote HSCs proliferation.Methodology: We constructed half-lethal-dose irradiation mouse models totest the blood cells amount changes. Then we detected chemokine CCL3&CXCL14concentration tendency in bone marrow microenvironment byELISA kit after IR, and we also used western blot to detect cathepsin G protein changes, which can hydrolyze chemokine CCL3.Results: We found that BMNC reparation was prior to WBC and PLT, butRBC amounts were stable during the bone marrow recovery phase. Afterdetecting the protein concentration in bone marrow, we found CCL3concentration has a significant decrease, while CXCL14concentrationmaintained stable. Cathepsin G, the hydrolytic enzyme that can hydrolyzeCCL3, in the whole bone marrow cells had a significant upregulation. Weconcluded that suppression of HSC proliferation was decreased through twopathways at least: downregulation of CCL3secretion spontaneously andincreasing CCL3proteolysis. Although CXCL14concentration remainsstable during recovery phase, which mRNA was significantly increased inour previous gene chip results, the protein result give us the possibility thatubiquitination regulates CXCL14concentration after IR injury and thisubiquitination effect may be related to tumorigenesis.Conclusions: We had a further study of previous gene chip results, dataprovided that chemokine CCL3as the key factor takes part in recoveryphase after IR injury and CXCL14does not participate in recovery processwhile it may be related to tumorigenesis. These results provide a referencefor the explanation of the pathological of IR recovery and the predictation ofdrug targets for further irradiation protection and drug development.