CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies
Abstract Background Traumatic brain injury (TBI) is a major cause of death and disability in the USA and the world; it constitutes 30% of injury-related deaths (Taylor et al., MMWR Surveill Summ 66:1-16, 2017). Contact sports athletes often experience repetitive TBI (rTBI), which exerts a cumulative...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-019-1499-z |
| _version_ | 1818922203718090752 |
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| author | Mahasweta Das Xiaolan Tang Jung Yeon Han Karthick Mayilsamy Elspeth Foran Manas R. Biswal Radouil Tzekov Shyam S. Mohapatra Subhra Mohapatra |
| author_facet | Mahasweta Das Xiaolan Tang Jung Yeon Han Karthick Mayilsamy Elspeth Foran Manas R. Biswal Radouil Tzekov Shyam S. Mohapatra Subhra Mohapatra |
| author_sort | Mahasweta Das |
| collection | DOAJ |
| description | Abstract Background Traumatic brain injury (TBI) is a major cause of death and disability in the USA and the world; it constitutes 30% of injury-related deaths (Taylor et al., MMWR Surveill Summ 66:1-16, 2017). Contact sports athletes often experience repetitive TBI (rTBI), which exerts a cumulative effect later in life. Visual impairment is a common after-effect of TBI. Previously, we have shown that C-C chemokine 20 (CCL20) plays a critical role in neurodegeneration and inflammation following TBI (Das et al., J Neuroinflammation 8:148, 2011). C-C chemokine receptor 6 (CCR6) is the only receptor that CCL20 interacts with. The objective of the present study was to investigate the role of CCL20-CCR6 axis in mediating rTBI-induced visual dysfunction (TVD). Methods Wild type (WT) or CCR6 knock out (CCR6−/−) mice were subjected to closed head rTBI. Pioglitazone (PG) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist which downregulates CCL20 production. Subsets of WT mice were treated with PG following final rTBI. A subset of mice was also treated with anti-CCL20 antibody to neutralize the CCL20 produced after rTBI. Histopathological assessments were performed to show cerebral pathologies, retinal pathologies, and inflammatory changes induced by rTBI. Results rTBI induced cerebral neurodegeneration, retinal degeneration, microgliosis, astrogliosis, and CCL20 expression. CCR6−/− mice showed reduced retinal degeneration, microgliosis, and inflammation. Treatment with CCL20 neutralization antibody or PG showed reduced CCL20 expression along with reduced retinal degeneration and inflammation. rTBI-induced GFAP-positive glial activation in the optic nerve was not affected by knocking out CCR6. Conclusion The present data indicate that rTBI-induced retinal pathology is mediated at least in part by CCL20 in a CCR6-dependent manner. |
| first_indexed | 2024-12-20T01:49:49Z |
| format | Article |
| id | doaj.art-29c624503c884ce1809039160d3a8413 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-20T01:49:49Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-29c624503c884ce1809039160d3a84132022-12-21T19:57:40ZengBMCJournal of Neuroinflammation1742-20942019-05-0116111210.1186/s12974-019-1499-zCCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologiesMahasweta Das0Xiaolan Tang1Jung Yeon Han2Karthick Mayilsamy3Elspeth Foran4Manas R. Biswal5Radouil Tzekov6Shyam S. Mohapatra7Subhra Mohapatra8James A. Haley Veterans HospitalJames A. Haley Veterans HospitalJames A. Haley Veterans HospitalJames A. Haley Veterans HospitalJames A. Haley Veterans HospitalGraduate Programs at College of Pharmacy, University of South FloridaJames A. Haley Veterans HospitalJames A. Haley Veterans HospitalJames A. Haley Veterans HospitalAbstract Background Traumatic brain injury (TBI) is a major cause of death and disability in the USA and the world; it constitutes 30% of injury-related deaths (Taylor et al., MMWR Surveill Summ 66:1-16, 2017). Contact sports athletes often experience repetitive TBI (rTBI), which exerts a cumulative effect later in life. Visual impairment is a common after-effect of TBI. Previously, we have shown that C-C chemokine 20 (CCL20) plays a critical role in neurodegeneration and inflammation following TBI (Das et al., J Neuroinflammation 8:148, 2011). C-C chemokine receptor 6 (CCR6) is the only receptor that CCL20 interacts with. The objective of the present study was to investigate the role of CCL20-CCR6 axis in mediating rTBI-induced visual dysfunction (TVD). Methods Wild type (WT) or CCR6 knock out (CCR6−/−) mice were subjected to closed head rTBI. Pioglitazone (PG) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist which downregulates CCL20 production. Subsets of WT mice were treated with PG following final rTBI. A subset of mice was also treated with anti-CCL20 antibody to neutralize the CCL20 produced after rTBI. Histopathological assessments were performed to show cerebral pathologies, retinal pathologies, and inflammatory changes induced by rTBI. Results rTBI induced cerebral neurodegeneration, retinal degeneration, microgliosis, astrogliosis, and CCL20 expression. CCR6−/− mice showed reduced retinal degeneration, microgliosis, and inflammation. Treatment with CCL20 neutralization antibody or PG showed reduced CCL20 expression along with reduced retinal degeneration and inflammation. rTBI-induced GFAP-positive glial activation in the optic nerve was not affected by knocking out CCR6. Conclusion The present data indicate that rTBI-induced retinal pathology is mediated at least in part by CCL20 in a CCR6-dependent manner.http://link.springer.com/article/10.1186/s12974-019-1499-zrTBICCL20PioglitazoneCCR6−/−RetinaRGC |
| spellingShingle | Mahasweta Das Xiaolan Tang Jung Yeon Han Karthick Mayilsamy Elspeth Foran Manas R. Biswal Radouil Tzekov Shyam S. Mohapatra Subhra Mohapatra CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies Journal of Neuroinflammation rTBI CCL20 Pioglitazone CCR6−/− Retina RGC |
| title | CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies |
| title_full | CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies |
| title_fullStr | CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies |
| title_full_unstemmed | CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies |
| title_short | CCL20-CCR6 axis modulated traumatic brain injury-induced visual pathologies |
| title_sort | ccl20 ccr6 axis modulated traumatic brain injury induced visual pathologies |
| topic | rTBI CCL20 Pioglitazone CCR6−/− Retina RGC |
| url | http://link.springer.com/article/10.1186/s12974-019-1499-z |
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