This Month in AJP
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This Month in AJP IkB Kinase-b Limits Immediate Hypersensitivity Pharmacological inhibitors of IkB kinase (IKK), espe- cially IKK-b, have been developed to treat inflammatory diseases. Using a murine allergic conjunctivitis model, Miyazaki et al (Am J Pathol 2013, 183:96e107) analyzed the effects of such pharmacological inhibition of IKK on mast cellemediated immediate hypersensitivity reactions. In vitro and in vivo analysis revealed that IKK-b limits B cellemediated mast cell activation and inflammatory cytokine induction in immediate hypersensitivity by counter-balancing the activity of IKK-a. Bisphenol A Causes Molar Incisor Hypomineralization Molar incisor hypomineralization (MIH) in children occurs concurrently with endocrine disrupting chemical (EDC)erelated pathologies. Jedeon et al (Am J Pathol 2013, 183:108e118) investigated the effect of bisphenol A (BPA), a typical EDC used in plastics and epoxy resin production, on amelogenesis in rats. Results document the first experimental MIH model and suggest that BPA exerts its effects on amelogenesis by disrupting normal protein removal from the enamel matrix, making MIH a marker for retrospective analysis of infant exposure to EDCs. Progenitors in Fibrotic Liver Regeneration Failure of fibrotic liver to regenerate after resection limits therapeutic options and increases demand for liver trans- plantation, posing a significant clinical problem. To gain insight into molecular mechanisms of regeneration in the context of fibrotic liver, Kuramitsu et al (Am J Pathol 2013, 182e194) characterized a murine model of partial hepatectomy of fibrotic liver and established a sequence of pathologic events associated with compromised fibrotic liver regeneration. Data suggest for the first time that therapeutic targeting of the profibrogenic progenitor (oval)ecell response represents a promising strategy to improve hepatectomy outcomes in patients with liver fibrosis. Role of Reversal Cells in Osteoporosis Osteoporosis may result from a failure during the bone formation phase that leads to incomplete refilling of resorption cavities or a failure at the reversal phase, uncoupling bone formation from resorption. Andersen et al (Am J Pathol 2013, 235e246) hypothesized that reversal cells may play a role in coupling bone resorption and formation. Data suggest that arrested reversal cells reflect aborted remodeling cycles that did not progress to the bone formation step. It is likely that bone loss in postmenopausal osteoporosis may result from both a failure of the bone formation step as commonly believed and a failure at the reversal step. Tamoxifen Elicits Atheroprotection Not Reendothelialization Tamoxifen, a drug used for hormonotherapy of estrogen receptor (ER)epositive breast cancers, has been proposed to have cardiovascular benefits. Using a mouse model deficient for ERa (ERa / LDL-r / ) or selectively deficient for its activating function (AF)e1(ERaAF-1 0/0 LDL-r / ), Fontaine et al (Am J Pathol 2013, 304e312) determined the involvement of ERa and AF-1 in mediating vasculo- protective action of tamoxifen. Tamoxifen appears to mediate its actions in vivo through the selective activation of ERaAF-1, which is sufficient to prevent atheroma but not to accelerate endothelial healing. Copyright ª 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajpath.2013.04.026 ajp.amjpathol.org The American Journal of Pathology, Vol. 183, No. 1, July 2013
Transcript of This Month in AJP
The American Journal of Pathology, Vol. 183, No. 1, July 2013
ajp.amjpathol.org
This Month in AJP
IkB Kinase-b Limits ImmediateHypersensitivity
Pharmacological inhibitors of IkB kinase (IKK), espe-cially IKK-b, have been developed to treat inflammatorydiseases. Using a murine allergic conjunctivitis model,Miyazaki et al (Am J Pathol 2013, 183:96e107) analyzedthe effects of such pharmacological inhibition of IKK onmast cellemediated immediate hypersensitivity reactions.In vitro and in vivo analysis revealed that IKK-b limits Bcellemediated mast cell activation and inflammatorycytokine induction in immediate hypersensitivity bycounter-balancing the activity of IKK-a.
Bisphenol A Causes Molar IncisorHypomineralization
Molar incisor hypomineralization (MIH) in childrenoccurs concurrently with endocrine disrupting chemical(EDC)erelated pathologies. Jedeon et al (Am J Pathol2013, 183:108e118) investigated the effect of bisphenolA (BPA), a typical EDC used in plastics and epoxy resinproduction, on amelogenesis in rats. Results document thefirst experimental MIH model and suggest that BPA exertsits effects on amelogenesis by disrupting normal proteinremoval from the enamel matrix, making MIH a markerfor retrospective analysis of infant exposure to EDCs.
Progenitors in Fibrotic Liver Regeneration
Failure of fibrotic liver to regenerate after resection limitstherapeutic options and increases demand for liver trans-plantation, posing a significant clinical problem. To gaininsight into molecular mechanisms of regeneration in thecontext of fibrotic liver, Kuramitsu et al (Am J Pathol2013, 182e194) characterized a murine model of partialhepatectomy of fibrotic liver and established a sequence
Copyright ª 2013 American Society for Investigative Pathology.
Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajpath.2013.04.026
of pathologic events associated with compromised fibroticliver regeneration. Data suggest for the first time thattherapeutic targeting of the profibrogenic progenitor(oval)ecell response represents a promising strategy toimprove hepatectomy outcomes in patients with liverfibrosis.
Role of Reversal Cells in Osteoporosis
Osteoporosis may result from a failure during the boneformation phase that leads to incomplete refilling ofresorption cavities or a failure at the reversal phase,uncoupling bone formation from resorption. Andersenet al (Am J Pathol 2013, 235e246) hypothesized thatreversal cells may play a role in coupling bone resorptionand formation. Data suggest that arrested reversal cellsreflect aborted remodeling cycles that did not progressto the bone formation step. It is likely that bone loss inpostmenopausal osteoporosis may result from both afailure of the bone formation step as commonly believedand a failure at the reversal step.
Tamoxifen Elicits Atheroprotection NotReendothelialization
Tamoxifen, a drug used for hormonotherapy of estrogenreceptor (ER)epositive breast cancers, has been proposedto have cardiovascular benefits. Using a mouse modeldeficient for ERa (ERa�/�LDL-r�/�) or selectively deficientfor its activating function (AF)e1 (ERaAF-10/0LDL-r�/�),Fontaine et al (Am J Pathol 2013, 304e312) determinedthe involvement of ERa and AF-1 in mediating vasculo-protective action of tamoxifen. Tamoxifen appears tomediate its actions in vivo through the selective activation ofERaAF-1, which is sufficient to prevent atheroma but not toaccelerate endothelial healing.
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