Background
Methods
Reagents
Animals, surgery, and therapy
Two-dimensional liquid chromatography/tandem mass spectrometry/mass spectrometry (2D-LC/MS/MS), proteomics, and pathway analysis
Real-time qRT-PCR, genome-wide transcriptional profiling, and pathway analysis
MMP-9 purification and proteolysis of MBP in vitro
Gelatin zymography
Neuropathology, immunohistochemistry, and microscopy
Behavior tests
Data analyses
Results
Proteomics identifies prominent Th cell signaling that follows nerve injury
Biological function |
Pvalue | Molecules |
---|---|---|
Infectious disease | 2.41E-03 to 4.67E-02 | AFG3L2, AHCTF1, ALKBH3, BCLAF1, C1R, DDX23, DPM1, ETHE1, FLII, GANAB, HLA-DQB1, IMPDH1, MAPT, MERTK, NUP62, PPP3CA, PPP3CB, PYCRL, RAB6A, RANBP2, RPL10A (includes EG:4736), SFRS2, STXBP1, STXBP1, TIMM8A, TOP2B, TPPP, TPPP, USP39, ZMPSTE24 |
CD28 signaling in T-helper cells | 1.25E-02 | FYN, HLA-DQB1, PDPK1, PPP3CA, PPP3CB, PTPN6 |
Calcium-induced T lymphocyte apoptosis | 3.87E-03 | ATP2A3, HLA-DQB1, PPP3CA, PPP3CB, PRKCI |
Acute MMP-2/9 inhibition blocks CCI-induced allodynia and neuroinflammation
MMP-9 degrades MBP in vitro and in vivo
ASQKRPSQR10 HGSKY↓LATAS20 TMDHARHGFL30 PRH↓RDTGILD40 SIGRFFGGDR50 GAPKRGSGKD60 SHHPARTAHY70 GSLPQKSHGR80 TQDENPVVHF90 F↓KN↓IVTP↓RTP100 PP↓SQGKGRGL110 SLSRFSWGAE120 GQRPGFGYGG130 RASD↓YKSAHK140 GFKGVDAQGT150 LSK↓IFKLGGR160 DSRSGSPMAR170 R171
| ||
---|---|---|
Peptide sequences | Molecular mass, Da | |
Calculated | Measured | |
A2SQKRPSQRHGSKYLATASTMDHARHGFLPRHRDTGILDSIGRFFGGD | 14,482 | 14,498 |
RGAPKRGSGKDSHHPARTAHYGSLPQKSHGRTQDENPVVHFFKNIVTP | ||
RTPPPSQGKGRGLSLSRFSWGAEGQRPGFGYGGRASD134
| ||
L16ATASTMDHARHGFLPRHRDTGILDSIGRFFGGDRGAPKRGSGKDSH | 10,229 | 10,247 |
HPARTAHYGSLPQKSHGRTQDENPVVHFFKNIVTPRTPPPSQGKGRG109
| ||
L16ATASTMDHARHGFLPRHRDTGILDSIGRFFGGDRGAPKRGSGKDSH | 8,357 | 8,356 |
HPARTAHYGSLPQKSHGRTQDENPVVHFF91
| ||
S103QGKGRGLSLSRFSWGAEGQRPGFGYGGRASDYKSAHKGFKGVDA | 7,307 | 7,296 |
QGTLSKIFKLGGRDSRSGSPMARR171
| ||
R34DTGILDSIGRFFGGDRGAPKRGSGKDSHHPARTAHYGSLPQKSH | 7,010 | 7,018 |
GRTQDENPVVHFFKNIVTP97
| ||
I94VTPRTPPPSQGKGRGLSLSRFSWGAEGQRPGFGYGGRASDYKSAHK | 6,293 | 6,284 |
GFKGVDAQGTLSK153
|
The endogenous MBP epitopes in Schwann cells, monocytes, and A-fibers of the injured nerve
MBP peptides induce allodynia
T cell deficiency diminishes the pro-nociceptive MBP84-104 action
Functions annotation | Nerve, -log (P value) | Spinal cord, -log (P value) | ||
---|---|---|---|---|
WT | Nude | WT | Nude | |
Immune response | 20.2 | - | 4.32 | - |
Inflammatory response | 15.8 | - | 2.79 | 1.42 |
Activation of T lymphocytes | 7.8 | - | 2.64 | - |
Chemotaxis/aggregation of APCs | 5.5 | 2.39 | 2.54 | 2.88 |
Chemotaxis of monocytes | 4.2 | 2.61 | 1.86 | 2.36 |