TNF-α and Phosphorylation of ERK in DRG and Spinal Cord

Takahashi, Naoto; Kikuchi, Shinichi; Shubayev, Veronica I.; Campana, W. Marie; Myers, Robert R.

doi:10.1097/01.brs.0000201305.01522.17

Cited by 53 publications

(24 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TNF-␣ regulates MAPKs and NF-B signaling pathways in cell lines and primary neuronal cultures (23,31,33,(42)(43)(44). In this report we show that TNF-␣ induces activation of ERK1/2, p38 MAPK, JNK, and NF-B signaling pathways in PC12 cells.…”

Section: Discussionmentioning

confidence: 54%

See 1 more Smart Citation

Tumor Necrosis Factor-α Regulates Cyclin-dependent Kinase 5 Activity during Pain Signaling through Transcriptional Activation of p35

Utreras

Futatsugi

Rudrabhatla

et al. 2009

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase. We have previously reported that Cdk5 participates in the regulation of nociceptive signaling, and the expression of Cdk5 and its activator, p35, are up-regulated in nociceptive neurons during peripheral inflammation. The aim of our current study was to identify the proinflammatory molecules that regulate Cdk5/p35 activity in response to inflammation. We constructed a vector that contains the mouse p35 promoter driving luciferase expression. We transiently transfected this vector in PC12 cells to test the effect of several cytokines on p35 transcriptional activity and Cdk5 activity. Our results indicate that tumor necrosis factor-␣ (TNF-␣) activates p35 promoter activity in a dose-and time-dependent manner and concomitantly up-regulates Cdk5 activity. Because TNF-␣ is known to activate ERK1/2, p38 MAPK, JNK, and NF-B signaling pathways, we examined their involvement in the activation of p35 promoter activity. MEK inhibitor, which inhibits ERK activation, decreased p35 promoter activity, whereas the inhibitors of p38 MAPK, JNK, and NF-〉 increased p35 promoter activity, indicating that these pathways regulate p35 expression differently. The mRNA and protein levels of Egr-1, a transcription factor, were increased by TNF-␣ treatment, and this increase was dependent on ERK signaling. In a mouse model of inflammation-induced pain in which carrageenan injection into the hind paw causes hypersensitivity to heat stimuli, TNF-␣ mRNA was increased at the site of injection. These findings suggest that TNF-␣-mediated regulation of Cdk5 activity plays an important role in inflammation-induced pain signaling.

show abstract

Section: Discussionmentioning

confidence: 54%

“…Activity-TNF-␣ is known to activate MAPK pathways, such as ERK1/2, p38 MAPK, JNK, and NF-B pathways (22,23,33). We examined the influence of these pathways on TNF-␣-mediated activation of p35 promoter activity.…”

Section: Tnf-␣-mediated Activation Of Erk1/2 P38 Mapk Jnk and Nf-bmentioning

confidence: 99%

Tumor Necrosis Factor-α Regulates Cyclin-dependent Kinase 5 Activity during Pain Signaling through Transcriptional Activation of p35

Utreras

Futatsugi

Rudrabhatla

et al. 2009

Journal of Biological Chemistry

108

View full text Add to dashboard Cite

show abstract

“…The proper balance of factors is essential to ensure the unique capacity of the PNS for regeneration (28). Imbalances may have severe consequences, including the development of chronic neuropathic pain states, associated with conditions such as sciatica (29,30). Neuropathic pain is refractory to analgesic therapy.…”

Section: Introductionmentioning

confidence: 99%

A shed form of LDL receptor–related protein–1 regulates peripheral nerve injury and neuropathic pain in rodents

Gaultier

Arandjelovic

et al. 2008

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

Injury to the peripheral nervous system (PNS) initiates a response controlled by multiple extracellular mediators, many of which contribute to the development of neuropathic pain. Schwann cells in an injured nerve demonstrate increased expression of LDL receptor-related protein-1 (LRP1), an endocytic receptor for diverse ligands and a cell survival factor. Here we report that a fragment of LRP1, in which a soluble or shed form of LRP1 with an intact α-chain (sLRP-α), was shed by Schwann cells in vitro and in the PNS after injury. Injection of purified sLRP-α into mouse sciatic nerves prior to chronic constriction injury (CCI) inhibited p38 MAPK activation (P-p38) and decreased expression of TNF-α and IL-1β locally. sLRP-α also inhibited CCI-induced spontaneous neuropathic pain and decreased inflammatory cytokine expression in the spinal dorsal horn, where neuropathic pain processing occurs. In cultures of Schwann cells, astrocytes, and microglia, sLRP-α inhibited TNF-α-induced activation of p38 MAPK and ERK/MAPK. The activity of sLRP-α did not involve TNF-α binding, but rather glial cell preconditioning, so that the subsequent response to TNF-α was inhibited. Our results show that sLRP-α is biologically active and may attenuate neuropathic pain. In the PNS, the function of LRP1 may reflect the integrated activities of the membrane-anchored and shed forms of LRP1.

show abstract

“…L'inflammation joue clairement un rôle majeur dans la pathogénie de nombreux troubles rachidiens tels que hernie discale et sciatique, deux troubles précédemment considérés comme principalement de nature mécanique ou dégénérative. 2 Les traits cliniques d'un SDRC aigu (vasodilatation, gonflement, changements de température locale, douleur) indiquent un processus d'inflammation localisée. Une réaction régionale inflammatoire exagérée est considérée responsable du mécanisme physiopathologique sous-jacent au SDRC par de nouvelles données.…”

unclassified

“…It is clear that inflammation plays a significant role in the pathogenesis of several spinal disorders, such as disc herniation and sciatica, which have previously been regarded as being primarily mechanical or degenerative in nature. 2 Clinical features of acute CRPS (vasodilatation, swelling, local temperature changes, pain) indicate a localized inflammatory process. New data support an exaggerated regional inflammatory response as the pathophysiological mechanism underlying CRPS.…”

mentioning

confidence: 99%

Is complex regional pain syndrome an inflammatory process? Theories and therapeutic implications

Taha

Blaise

2007

Can J Anesth/J Can Anesth

View full text Add to dashboard Cite

TNF-α and Phosphorylation of ERK in DRG and Spinal Cord

Abstract: These findings suggest that ERK signaling plays a role in the activation of DRG cells following inflammatory injuries to nerve roots and further documents the importance of inflammation in the pathogenesis of painful spine disorders.

Cited by 53 publications

References 54 publications

Tumor Necrosis Factor-α Regulates Cyclin-dependent Kinase 5 Activity during Pain Signaling through Transcriptional Activation of p35

Tumor Necrosis Factor-α Regulates Cyclin-dependent Kinase 5 Activity during Pain Signaling through Transcriptional Activation of p35

A shed form of LDL receptor–related protein–1 regulates peripheral nerve injury and neuropathic pain in rodents

Is complex regional pain syndrome an inflammatory process? Theories and therapeutic implications

Contact Info

Product

Resources

About