[Corrigendum] Cryptotanshinone inhibits IgE­mediated degranulation through inhibition of spleen tyrosine kinase and tyrosine­protein kinase phosphorylation in mast cells.

Following the publication of the above article, an interested reader drew to the authors' attention that they had mentioned that activated PKCδ phosphorylates IKKß in order that IKKß is relocated to the plasma membrane, resulting in the induction of mast cell degranulation; however, four references the authors had included did not seem to support this statement. The authors have re-examined their paper, and realized that the four references the reader mentioned were indeed cited incorrectly, and wish to rectify this error through revising the third paragraph in the Discussion section, the References section, and an associated figure (Fig. 6C) in order to avoid any further misunderstandings on the part of the readership. First, the authors wish to revise the wording of the third and fourth paragraphs of the Discussion, as featured on pp. 1101-1102, to the following (changed text is indicated in bold): 'We showed that CRT exerts anti-AD effect through inhibition of the mast cell degranulation in mast cells. Upon IgE/antigen stimulation, the immunoreceptor tyrosine-based activation motif (ITAM) region of FcεRI receptor which is on the mast cell surface is phosphorylated and the initial signalling protein kinases Lyn and Syk are recruited to the ITAM (28,29). Then, the activated Lyn and Syk leads to phosphorylation of the transmembrane adaptor linker for activation of T cells (LAT). Phosphorylated LAT which is a scaffold for multimolecular signalling complexes and activates PLCγ through phosphorylation. The activated PLCγ hydrolyses phosphatidylinositol biphosphate (PIP2) to generate second signalling molecules IP3 and DAG, which activate PKCs including PKCδ to induce the mast cell degranulation (30,31). On the other hand, cross-linking of FcεRI also activates IKKß, which moves to the lipid raft fractions and phosphorylates synaptosomal-associated protein 23 (SNAP-23) leading to degranulation (7). Since PKCδ phosphorylates IKKα, but not IKKß (32), it is not likely that two signalling pathways are directly connected. In this study, novel function of CRT on phosphorylations of Lyn/Syk kinases in mast cells is elucidated for the first time. Furthermore, it is likely that this inhibitory effect of CRT on Lyn/Syk kinases negatively affected activities of their downstream signalling molecules including PLCγ, PKCδ, and IKKß, which leads to decrease in mast cell degranulation by CRT treatment. Besides the inhibitory effect of CRT on mast cell degranulation, here we provide additional evidence that CRT exerts anti-AD effects through inactivation of MAPK and NF­κB. It has been reported that CRT regulates the activities of MAPK and NF­κB in various cell types. In rhabdomyosarcoma, hepatoma, and breast carcinoma, CRT activates MAPK p38/JNK and suppresses ERK1/2, followed by caspase-independent apoptosis (10,33,34). In chronic myeloid leukaemia cells, CRT enhances TNF­α-induced apoptosis through the activation of MAPK p38 (35). In smooth muscle cells, CRT exerts anti-migration/invasion effect as it inhibits TNF­α/NF­κB signalling pathway (36).' Secondly, the authors wish to make the following changes to the Reference list: New references 30-32 have been inserted to the list, as follows: 30. Ozawa K, Szallasi Z, Kazanietz MG, Blumberg PM, Mischak H, Mushinski JF and Beaven MA: Ca2+-dependent and Ca2+-independent isozymes of protein kinase C mediate exocytosis in antigen-stimulated rat basophilic RBL-2H3 cell. J Biol Chem 268: 1749-1756, 1993. 31. Cho SH, Woo CH, Yoon SB and Kim JH: Protein kinase Cδ functions downstream of Ca2+ mobilization in FcεRI signaling to degranulation in mast cells. J Allergy Clin Immunol 114: 1085-1092, 2004. 32. Yamaguchi T, Miki Y and Yoshida K: Protein kinase Cδ activates IκB-kinase α to induce the p53 tumor suppressor in response to oxidative stress. Cell Signal 19: 2088-2097, 2007. The addition of these new references means that the former references 30-33 have been accordingly renumbered to references 33-36. Finally, the authors have revised Fig. 6C, as it appeared on p. 1102, in order to assist the understanding of the readers, and the corrected version of Fig. 6 appears on the next page. All these corrections have been approved by all the authors, with the exception of the first author, Sumiyasuren Buyanravjikh, who is no longer uncontactable. The authors regret that these errors were included in the paper, even though they did not substantially alter any of the major conclusions reported in the study, are grateful to the Editor for allowing them this opportunity to publish a Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 18: 1095­1193, 2018; DOI: 10.3892/mmr.2018.9042].

C1q/TNF-α-Related Protein 1 (CTRP1) Maintains Blood Pressure Under Dehydration Conditions.

RATIONALE: Circulating CTRP1 (C1q/TNF-α [tumor necrosis factor-α]-related protein 1) levels are increased in hypertensive patients compared with those in healthy subjects. Nonetheless, little is known about the molecular and physiological function of CTRP1 in blood pressure (BP) regulation. OBJECTIVE: To investigate the physiological/pathophysiological role of CTRP1 in BP regulation. METHODS AND RESULTS: CTRP1 production was increased to maintain normotension under dehydration conditions, and this function was impaired in inducible CTRP1 KO (knockout) mice (CTRP1 ΔCAG). The increase in CTRP1 under dehydration conditions was mediated by glucocorticoids, and the antagonist mifepristone prevented the increase in CTRP1 and attenuated BP recovery. Treatment with a synthetic glucocorticoid increased the transcription, translation, and secretion of CTRP1 from skeletal muscle cells. Functionally, CTRP1 increases BP through the stimulation of the AT1R (Ang II [angiotensin II] receptor 1)-Rho (Ras homolog gene family)/ROCK (Rho kinase)-signaling pathway to induce vasoconstriction. CTRP1 promoted AT1R plasma membrane trafficking through phosphorylation of AKT and AKT substrate of 160 kDa (AS160). In addition, the administration of an AT1R blocker, losartan, recovered the hypertensive phenotype of CTRP1 TG (transgenic) mice. CONCLUSIONS: For the first time, we provide evidence that CTRP1 contributes to the regulation of BP homeostasis by preventing dehydration-induced hypotension.

Erratum: Eupatolide inhibits the TGF-ß1-induced migration of breast cancer cells via downregulation of SMAD3 phosphorylation and transcriptional repression of ALK5.

[This corrects the article DOI: 10.3892/ol.2017.6957.].

Cryptotanshinone inhibits IgE­mediated degranulation through inhibition of spleen tyrosine kinase and tyrosine­protein kinase phosphorylation in mast cells.

Atopic dermatitis (AD) is a type of chronic skin inflammation and one of the most common relapsing allergic diseases, which presents with a severe rash and itchy skin lesions. The pathogenesis of AD is primarily associated with hyper­activated mast cells, which makes them an effective treatment target. After cross­linking the antigen/immunoglobulin (Ig) E complex binds to its high affinity receptor FcεRl on the surface of mast cells. The cells subsequently secrete excessive pro­inflammatory mediators, including histamine and cytokines, which lead to pruritus and immune cell infiltration in the skin lesions. The present study screened natural compounds that have an inhibitory effect on IgE/antigen­mediated secretory activity. It was revealed that cryptotanshinone (CRT), a natural compound extracted from Salvia miltiorrhiza Bunge, had inhibitory effects on the IgE/antigen complex. The underlying mechanism by which CRT exerted an anti­allergy/inflammatory function was investigated using rat basophilic leukaemia (RBL) cells for degranulation assays and a 1­chloro­2,4­dinitrobenzene (DNCB)­induced AD Balb/c mouse model for in vivo study. CRT effectively mitigated the secretion of pro­inflammatory cytokines, including tumor necrosis factor­α and interleukin 1ß, as well as immune cell infiltration into skin lesions in a mouse model of AD­like skin disease induced by dinitrochlorobenzene. The inhibitory effect of CRT on IgE­mediated mast cell degranulation was mediated by the inhibition of tyrosine kinase­dependent degranulation signalling pathways involving spleen tyrosine kinase and Lyn. The present study revealed CRT as an inhibitor of mast cell degranulation. Therefore, CRT may be considered for development as a therapeutic drug to treat IgE­mediated skin diseases.

Eupatolide inhibits the TGF-ß1-induced migration of breast cancer cells via downregulation of SMAD3 phosphorylation and transcriptional repression of ALK5.

The epithelial-mesenchymal transition (EMT) is a hallmark of cancer metastasis, and the associated molecular signaling pathways are regarded as therapeutic targets for cancer treatment. Thus, suppressing EMT with a natural chemical compound may be of therapeutic benefit. Eupatolide is a natural chemical compound extracted from the medicinal plant Inula britannica, which is used in Eastern Asia to treat bronchitis, disorders of the digestive system and inflammation. Besides the anti-inflammatory function of eupatolide, the present study found that eupatolide suppressed the migration and invasion of breast cancer cells, which was associated with the downregulation of vimentin in MDA-MB-231 cells and the upregulation of E-cadherin in MCF-7 cells. Treatment with eupatolide also significantly inhibited the migration and invasion of breast cancer cells that had been stimulated with transforming growth factor-ß1 (TGF-ß1). Eupatolide also suppressed TGF-ß1-induced EMT via downregulation of mothers against decapentaplegic homolog 3 (SMAD3) phosphorylation and transcriptional repression of TGF-ß receptor 1 (ALK5). In addition to this canonical pathway, the non-canonical protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) pathways were also inhibited by eupatolide treatment. In summary, the results suggest that eupatolide suppresses the migration and invasion of breast cancer cells by blocking the canonical ALK5-SMAD3 signaling pathway and the non-canonical ERK and AKT signaling pathways.