Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis.
We have studied temporal mRNA expression patterns for interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), macrophage colony stimulating factor (M-CSF), and transforming growth factor-beta1 (TGF-beta1) in two rat injury paradigms with very different cellular inflammatory reactions: contussion of the spinal cord and axotomy of the facial nerve. Our comparative analyses using semiquantitative reverse transcription polymerase chain reaction (RT-PCR) show an early and robust upregulation of IL-1beta, TNF-alpha, IL-6, and M-CSF mRNAs in spinal cord after contusion injury. Peak expression of these mRNAs was transient and returned to control levels by 24 h postinjury. In contrast, expression of IL-1beta and TNF-alpha mRNAs in the axotomized facial nucleus was minimal and delayed, and levels of M-CSF mRNA remained unaltered. Similar to injured spinal cord, the axotomized nucleus showed a dramatic and early upregulation of IL-6 mRNA, but unlike spinal cord, IL-6 mRNA levels subsided only gradually. Both injury paradigms showed gradually increasing levels of TGF-beta1 mRNA which were maximal at 7 days postinjury. RT-PCR analyses were also performed on isolated blood-borne mononuclear cells and neutrophils. The results showed that these cells contain high levels of IL-1beta and M-CSF mRNAs, moderate levels of TGF-beta and TNF-alpha mRNAs, and minimal levels of IL-6 mRNA. The RT-PCR analyses together with histological observations indicate that expression of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 is short-lived and self-limited after contusion injury, and that it occurs primarily within endogenous glial cells. Transient expression of these molecules likely triggers secondary events which may be beneficial to wound repair and regeneration.
College of Medicine, University of Florida, Gainesville, Florida, 32610, USA.
W J
WJ
Streit
S L
SL
Semple-Rowland
S D
SD
Hurley
R C
RC
Miller
P G
PG
Popovich
B T
BT
Stokes
D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy; D003288:Contusions / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005154:Facial Nerve / Q000502:physiology*; D005260:Female; D005911:Gliosis / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D009414:Nerve Growth Factors / Q000096:biosynthesis; D009416:Nerve Regeneration / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D013119:Spinal Cord Injuries / Q000378:metabolism*
D016207:Cytokines; D009414:Nerve Growth Factors; D012333:RNA, Messenger