PMID- 12693669
OWN - NLM
STAT- MEDLINE
DCOM- 20031212
LR  - 20190607
IS  - 0963-6897 (Print)
IS  - 0963-6897 (Linking)
VI  - 12
IP  - 1
DP  - 2003
TI  - Tumor necrosis factor-alpha (TNF-alpha) stimulates chemotactic response in mouse 
      myogenic cells.
PG  - 91-100
AB  - Migration of transplanted myogenic cells occurs during both embryogenesis and 
      regeneration of skeletal muscles and is important for successful myoblast 
      transplantation, but little is known about factors that promote chemotaxis of 
      these cells. Tumor necrosis factor-alpha (TNF-alpha) is known to induce 
      chemotactic effect on several cell types. In this study, we investigated its 
      influence on the in vitro and in vivo motility of C2C12 and primary myoblasts. In 
      the in vitro test performed in the blind-well Boyden chambers, we showed that 
      TNF-alpha (50-400 U/ml) significantly enhanced the ability of myogenic cells to 
      migrate. The dose-response curve for this factor was bell shaped, with maximum 
      activity in the 200 U/ml range. In the in vivo test, intramuscular administration 
      of TNF-alpha was performed by an Alzet pump connected to a perforated 
      polyethylene microtube inserted in the tibialis anterior (TA) of CD1 mice. In 
      these experiments, myoblasts were injected under the muscle epimysium. The 
      recipient mice were immunosuppressed with FK506. Our results showed that, 5 days 
      after myoblast transplantation, cells migrated further in the muscles infused 
      with TNF-alpha than in the muscles not exposed to TNF-alpha. TNF-alpha not only 
      has a chemotactic activity but may also modify cell migration via its action on 
      matrix metalloproteinase (MMP) expression. The proteolytic activities of the MMPs 
      secreted in the muscles were thus also assessed by gelatin zymography. The 
      results showed an increased of MMP-2 and MMP-9 transcripts in the 
      TNF-alpha-infused muscles injected with myogenic cells. Myoblast migration during 
      transplantation may be enhanced by overlapping gradients of several effector 
      molecules such as TNF-alpha, interferon-gamma (INF-gamma), and interleukins, 
      released at the site of muscle injury. We propose that TNF-alpha may promote 
      myoblast migration directly through chemotactic activity and indirectly by 
      enhancing MMP activity at the site of muscle injury.
FAU - Torrente, Y
AU  - Torrente Y
AD  - Centro Dino Ferrari, Institute of Clinical Neurology, University of Milan, Milan, 
      Italy.
FAU - El Fahime, E
AU  - El Fahime E
FAU - Caron, N J
AU  - Caron NJ
FAU - Del Bo, R
AU  - Del Bo R
FAU - Belicchi, M
AU  - Belicchi M
FAU - Pisati, F
AU  - Pisati F
FAU - Tremblay, J P
AU  - Tremblay JP
FAU - Bresolin, N
AU  - Bresolin N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Lymphocyte Function-Associated Antigen-1)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects/*physiology
MH  - Cells, Cultured
MH  - Chemotaxis/drug effects/*physiology
MH  - Cytokines/immunology/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Immunosuppressive Agents/pharmacology
MH  - Lymphocyte Function-Associated Antigen-1/drug effects/metabolism
MH  - Macrophage-1 Antigen/drug effects/metabolism
MH  - Matrix Metalloproteinases/drug effects/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle, Skeletal/drug effects/injuries/*metabolism
MH  - Muscular Diseases/*therapy
MH  - Myoblasts/drug effects/metabolism/*transplantation
MH  - Tissue Transplantation/*methods
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
EDAT- 2003/04/16 05:00
MHDA- 2003/12/13 05:00
CRDT- 2003/04/16 05:00
PHST- 2003/04/16 05:00 [pubmed]
PHST- 2003/12/13 05:00 [medline]
PHST- 2003/04/16 05:00 [entrez]
AID - 10.3727/000000003783985115 [doi]
PST - ppublish
SO  - Cell Transplant. 2003;12(1):91-100. doi: 10.3727/000000003783985115.