Activation of p38 and ERK Signaling during Adenovirus Vector Cell Entry Lead to Expression of the C-X-C Chemokine IP-10

Tibbles, Lee Anne; Spurrell, Jason; Bowen, Gloria P.; Liu, Qiang; Lam, Mai T.; Zaiss, Anne K.; Robbins, Stephen M.; Hollenberg, Morley D.; Wickham, Thomas J.; Muruve, Daniel A.

doi:10.1128/jvi.76.4.1559-1568.2002

Cited by 118 publications

(136 citation statements)

References 49 publications

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“…The events involved in virus entry into a cell activate a number of second messenger pathways and signaling molecules. Downstream effects of signaling include the induction of adhesion molecules and multiple chemokines such as RANTES, IP-10, MIP-2, MCP-1 (32,33). In the current cardiac transplant model, the adenovirus vector induced multiple potent chemokines in transduced grafts, with IP-10 induced as early as day 1; MCP-1, MIP-1a, MIP-2 on day 3, and many more chemokines by day 7.…”

Section: Discussionmentioning

confidence: 89%

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Chen

Ding

Schröppel

et al. 2003

American Journal of Transplantation

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Transplantation of allogeneic grafts presents several challenges to the innate and adaptive immune systems including chemokine leukocyte recruitment, activation, and effector function. We defined the chemokines and receptors induced by the transplant procedure/ischemia injury, alloantigen and gene transfer vector administration in murine cardiac grafts. E1, E3 deleted AdRSVbgal was transferred into grafts at the time of transplantation, grafts were harvested after 1-14 days, and a pathway-specific cDNA array was used to evaluate the levels of 67 chemokine and chemokine receptor genes. Transplantation resulted in ischemic injury and induction of a number of similar genes in both the syngeneic and allogeneic grafts, such as CXCL1 and CXCL5, which increased dramatically on day 1 and returned rapidly to baseline in the syngeneic grafts. Alloantigen stimulated the adaptive immune response and induced the presence of more inflammatory genes within the grafts, particularly at later time points. The adenovirus vector induced a broader panel of genes, among them potent inflammatory chemokines CXCL9 and CXCL10, that are induced earlier or more strongly compared with alloantigen stimulation alone. As alloantigen and adenovirus vectors both induce similar sets of genes, targeting these molecules may not only inhibit alloimmunity, but also enhance the utility of the gene transfer vector.

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Section: Discussionmentioning

confidence: 89%

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Chen

Ding

Schröppel

et al. 2003

American Journal of Transplantation

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“…20 The very rapid increase in cytokine secretion and fever makes viral protein expression an unlikely explanation for these responses. Similar very rapid increases in the levels of mRNA for IL-8, and stimulation of signal transduction pathways, [24][25][26][27][28] suggest that the earliest phase (1-2 h) of inflammatory response to adenoviral vectors, both in nervous tissue as well as in other tissues, is independent of viral vector expression. Thus, the adenoviral capsid on its own may cause, through direct interactions at the membrane of target cells, stimulation of pro-inflammatory signalling cascades resulting in cytokine release.…”

Section: Brain Inflammation Upon Injection Of Viral Vectorsmentioning

confidence: 99%

Inflammation and adaptive immune responses to adenoviral vectors injected into the brain: peculiarities, mechanisms, and consequences

Löwenstein

Castro

2003

Gene Ther

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“…The underlying reasons for this will require further investigation, but it is possible that the ability of adenovirus type-5 vectors to elicit potent innate immune responses and local inflammatory reactions, which are essential in initiating primary immune responses, plays a role in this process [64][65][66].…”

Section: Discussionmentioning

confidence: 99%

HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime

Duke

Maguire

Keefer

et al. 2007

Vaccine

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HSV-1 amplicon vectors elicit strong T-cell responses to encoded antigens but the qualitative nature of these responses is poorly understood. Antigen-specific CD4 + and CD8 + T-cell responses to amplicon and adenovirus (rAd5) vectors encoding HIV-1 gp120 were assessed following immunization of mice, by performing intracellular cytokine staining for IFNγ, IL-2 and TNFα, following stimulation of splenocytes with a HIV-1 Env peptide pool. The quality of the primary Tcell response to amplicon and rAd5 vectors was strikingly similar, but there were qualitative differences in responses to amplicon vectors that incorporated different promoters upstream of gp120 -suggesting that promoters can significantly influence immune response quality. When prime-boost combinations were studied, a rAd5 prime and amplicon boost elicited the highest T-cell response. Furthermore, protocols that incorporated a rAd5 prime consistently elicited a greater proportion of polyfunctional CD4 + T-cells -regardless of boost. This suggests that initial priming can shape immune response quality after a boost. Overall, these findings provide insight into effective vector combinations for HIV-1 vaccine development.

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Activation of p38 and ERK Signaling during Adenovirus Vector Cell Entry Lead to Expression of the C-X-C Chemokine IP-10

Cited by 118 publications

References 49 publications

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Differential Chemokine and Chemokine Receptor Gene Induction by Ischemia, Alloantigen, and Gene Transfer in Cardiac Grafts

Inflammation and adaptive immune responses to adenoviral vectors injected into the brain: peculiarities, mechanisms, and consequences

HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime

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