PMID- 35670184
OWN - NLM
STAT- MEDLINE
DCOM- 20220816
LR  - 20221207
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 70
IP  - 10
DP  - 2022 Oct
TI  - Cathelicidin-related antimicrobial peptide promotes neuroinflammation through 
      astrocyte-microglia communication in experimental autoimmune encephalomyelitis.
PG  - 1902-1926
LID - 10.1002/glia.24227 [doi]
AB  - Cathelicidin-related antimicrobial peptide (CRAMP) is an effector molecule of the 
      innate immune system with direct antimicrobial and immunomodulatory activities; 
      however, its role in neuroinflammatory responses and related diseases is not 
      clearly understood. In particular, the expression of CRAMP and its functional 
      role has not been previously studied in experimental autoimmune encephalomyelitis 
      (EAE) or multiple sclerosis (MS). Here, we investigated the role of CRAMP in 
      neuroinflammation, using an EAE mouse model of MS and postmortem patient tissues. 
      We found that the CRAMP expression was increased in the spinal cords of 
      EAE-induced mice. Immunofluorescence analysis revealed that CRAMP is mainly 
      induced in reactive astrocytes in the inflamed spinal cord of EAE mice. A similar 
      pattern of the LL-37 (human CRAMP) expression was observed in the brain and 
      spinal cord tissues of patients with MS. An intrathecal injection of the CRAMP 
      peptide in EAE mice accelerated the onset of symptoms and increased disease 
      severity with augmented expression of inflammatory mediators, glial activation, 
      infiltration of inflammatory cells, and demyelination. In addition, 
      shRNA-mediated knockdown of Cramp in the spinal cord resulted in a milder disease 
      course with less inflammation in EAE mice. We identified FPR2 on microglia as a 
      CRAMP receptor and demonstrated that CRAMP potentiates IFN-gamma-induced microglial 
      activation via the STAT3 pathway. Taken together, our findings suggest that CRAMP 
      is a novel mediator of astrocyte-microglia interactions in neuroinflammatory 
      conditions such as EAE. Thus, CRAMP could be exploited as a biomarker or 
      therapeutic target for the diagnosis or treatment of MS.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Bhusal, Anup
AU  - Bhusal A
AD  - Department of Pharmacology, School of Medicine, Kyungpook National University, 
      Daegu, Republic of Korea.
AD  - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, 
      School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
FAU - Nam, Youngpyo
AU  - Nam Y
AD  - Department of Pharmacology, School of Medicine, Kyungpook National University, 
      Daegu, Republic of Korea.
FAU - Seo, Donggun
AU  - Seo D
AD  - Department of Pharmacology, School of Medicine, Kyungpook National University, 
      Daegu, Republic of Korea.
FAU - Rahman, Md Habibur
AU  - Rahman MH
AD  - Department of Pharmacology, School of Medicine, Kyungpook National University, 
      Daegu, Republic of Korea.
AD  - Division of Endocrinology, Department of Medicine, Rutgers Robert Wood Johnson 
      Medical School, New Brunswick, New Jersey, USA.
FAU - Hwang, Eun Mi
AU  - Hwang EM
AD  - Brain Science Institute, Korea Institute of Science and Technology, Seoul, 
      Republic of Korea.
FAU - Kim, Seung-Chan
AU  - Kim SC
AD  - Brain Science Institute, Korea Institute of Science and Technology, Seoul, 
      Republic of Korea.
FAU - Lee, Won-Ha
AU  - Lee WH
AD  - School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook 
      National University, Daegu, Republic of Korea.
FAU - Suk, Kyoungho
AU  - Suk K
AUID- ORCID: 0000-0002-9555-4203
AD  - Department of Pharmacology, School of Medicine, Kyungpook National University, 
      Daegu, Republic of Korea.
AD  - BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, 
      School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
AD  - Brain Science and Engineering Institute, Kyungpook National University, Daegu, 
      Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220607
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Antimicrobial Cationic Peptides)
RN  - 0 (Antimicrobial Peptides)
RN  - 0 (Cathelicidins)
SB  - IM
MH  - Animals
MH  - Antimicrobial Cationic Peptides
MH  - Antimicrobial Peptides
MH  - Astrocytes/metabolism
MH  - Communication
MH  - *Encephalomyelitis, Autoimmune, Experimental/drug therapy/metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/metabolism
MH  - *Multiple Sclerosis/metabolism
MH  - Neuroinflammatory Diseases
MH  - Spinal Cord/metabolism
MH  - Cathelicidins
OTO - NOTNLM
OT  - astrocyte
OT  - cathelicidin
OT  - formyl peptide receptor
OT  - microglia
OT  - multiple sclerosis
OT  - neuroinflammation
EDAT- 2022/06/08 06:00
MHDA- 2022/08/17 06:00
CRDT- 2022/06/07 04:33
PHST- 2022/05/10 00:00 [revised]
PHST- 2021/11/17 00:00 [received]
PHST- 2022/05/25 00:00 [accepted]
PHST- 2022/06/08 06:00 [pubmed]
PHST- 2022/08/17 06:00 [medline]
PHST- 2022/06/07 04:33 [entrez]
AID - 10.1002/glia.24227 [doi]
PST - ppublish
SO  - Glia. 2022 Oct;70(10):1902-1926. doi: 10.1002/glia.24227. Epub 2022 Jun 7.