PMID- 18375741
OWN - NLM
STAT- MEDLINE
DCOM- 20080721
LR  - 20200930
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 294
IP  - 6
DP  - 2008 Jun
TI  - Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated 
      by splice variant A.
PG  - L1187-96
LID - 10.1152/ajplung.00388.2007 [doi]
AB  - Chemokine receptors control several fundamental cellular processes in both 
      hematopoietic and structural cells, including directed cell movement, i.e., 
      chemotaxis, cell differentiation, and proliferation. We have previously 
      demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory 
      cells present in the lung, is also expressed by human airway epithelial cells. In 
      airway epithelial cells, activation of CXCR3 induces airway epithelial cell 
      movement and proliferation, processes that underlie lung repair. The present 
      study examined the expression and function of CXCR3 in human alveolar type II 
      pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal 
      and adult type II pneumocytes as assessed by immunocytochemistry, 
      immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA 
      was present constitutively in cultured type II cells, but levels of CXCR3-B 
      greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig 
      induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line 
      produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did 
      not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, 
      I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated 
      kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B 
      kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 
      receptor is expressed by human type II pneumocytes, and the CXCR3-A splice 
      variant mediates chemotactic responses possibly through Ca(2+) activation of both 
      mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression 
      of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from 
      injury.
FAU - Ji, Rong
AU  - Ji R
AD  - Division of Pulmonary Disease and Critical Care Medicine, Department of Medicine, 
      Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
FAU - Lee, Clement M
AU  - Lee CM
FAU - Gonzales, Linda W
AU  - Gonzales LW
FAU - Yang, Yi
AU  - Yang Y
FAU - Aksoy, Mark O
AU  - Aksoy MO
FAU - Wang, Ping
AU  - Wang P
FAU - Brailoiu, Eugen
AU  - Brailoiu E
FAU - Dun, Nae
AU  - Dun N
FAU - Hurford, Matthew T
AU  - Hurford MT
FAU - Kelsen, Steven G
AU  - Kelsen SG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080328
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (CXCR3 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CXCR3)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adult
MH  - Alternative Splicing
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chemotaxis/*physiology
MH  - Dexamethasone/pharmacology
MH  - Humans
MH  - Lung/*cytology/embryology/immunology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Pneumonia/*physiopathology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, CXCR3/*physiology
MH  - Transfection
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2008/04/01 09:00
MHDA- 2008/07/22 09:00
CRDT- 2008/04/01 09:00
PHST- 2008/04/01 09:00 [pubmed]
PHST- 2008/07/22 09:00 [medline]
PHST- 2008/04/01 09:00 [entrez]
AID - 00388.2007 [pii]
AID - 10.1152/ajplung.00388.2007 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2008 Jun;294(6):L1187-96. doi: 
      10.1152/ajplung.00388.2007. Epub 2008 Mar 28.