Local production of serum amyloid a is implicated in the induction of macrophage chemoattractants in Schwann cells during wallerian degeneration of peripheral nerves.
The elevation of serum levels of serum amyloid A (SAA) has been regarded as an acute reactive response following inflammation and various types of injuries. SAA from the liver and extrahepatic tissues plays an immunomodulatory role in a variety of pathophysiological conditions. Inflammatory cytokines in the peripheral nerves have been implicated in the Wallerian degeneration of peripheral nerves after injury and in certain types of inflammatory neuropathies. In the present study, we found that a sciatic nerve axotomy could induce an increase of SAA1 and SAA3 mRNA expression in sciatic nerves. Immunohistochemical staining showed that Schwann cells are the primary sources of SAA production after nerve injury. In addition, interleukin-6-null mice, but not tumor necrosis factor-α-null mice showed a defect in the production of SAA1 in sciatic nerve following injury. Dexamethasone treatment enhanced the expression and secretion of SAA1 and SAA3 in sciatic nerve explants cultures, suggesting that interleukin-6 and corticosteroids might be major regulators for SAA production in Schwann cells following injury. Moreover, the stimulation of Schwann cells with SAA1 elicited the production of the macrophage chemoattractants, Ccl2 and Ccl3, in part through a G-protein coupled receptor. Our findings suggest that locally produced SAA might play an important role in Wallerian degeneration after peripheral nerve injury.
Department of Physiology, Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan, South Korea.
So Young
SY
Jang
Yoon Kyung
YK
Shin
Ha Young
HY
Lee
Joo Youn
JY
Park
Duk Joon
DJ
Suh
Jong Kuk
JK
Kim
Yoe-Sik
YS
Bae
Hwan Tae
HT
Park
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019771:Axotomy; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D002630:Chemotactic Factors / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D015850:Interleukin-6 / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology*; D020426:Sciatic Neuropathy / Q000150:complications / Q000209:etiology / Q000473:pathology; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D002630:Chemotactic Factors; D015850:Interleukin-6; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; C489995:Saa2 protein, mouse; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha; C481578:formyl peptide receptor 2, mouse; D003907:Dexamethasone