Background: IL-32␣ is known to interact with FAK1, and IL-32␣ overexpression in chronic myeloid leukemia cells increases natural killer cell-mediated killing. Results: IL-32␣ interacted with PKC⑀ and STAT3, mediated STAT3 phosphorylation, and thereby augmented IL-6 production. Conclusion: IL-32␣ elevated IL-6 production through interaction with PKC⑀ and STAT3. Significance: The interaction of IL-32␣ with PKC⑀ and STAT3 reveals a new intracellular mediatory role of IL-32␣.

No abstract

Luteolin is a common flavonoid that exists in medicinal herbs, fruits, and vegetables. Luteolin has biochemical functions including anti-allergy, anti-inflammation, and anti-cancer functions. However, its efficacy and precise mode of action against breast cancer are still under study. To elucidate whether luteolin exhibits an anticancer effect in breast cancer, MCF-7 breast cancer cells were incubated with luteolin, and apoptosis was assessed by observing nuclear morphological changes and by performing cell viability assay, cell cycle analysis, annexin V-FITC/PI double staining, western blotting, RT-PCR, and mitochondrial membrane potential measurements. Luteolin inhibited growth through perturbation of cell cycle progression at the sub-G1 and G1 phases in MCF-7 cells. Furthermore, luteolin enhanced the expression of death receptors, such as DR5, and activated caspase cascades. It enhanced the activities of caspase-8/-9/-3 in a dose-dependent manner, followed by inactivation of PARP. Activation of caspase-8 and caspase-9 induced caspase-3 activity, respectively, in apoptosis of extrinsic and intrinsic pathways. Luteolin also induced mitochondrial membrane potential collapse and cytochrome c release, and increased Bax expression by inhibiting expression of Bcl-2. Taken together, these results suggest that luteolin provokes cell cycle arrest and induces apoptosis by activating the extrinsic and intrinsic pathways.

Background: IL-32␤ promotes IL-10 production in myeloid cells. Results: IL-32␤-mediated C/EBP␣ serine 21 phosphorylation by PKC␦ induced the dissociation of C/EBP␣ from IL-10 promoter, thereby promoting IL-10 production. Conclusion: IL-32␤ suppressed the inhibitory effect of C/EBP␣ on IL-10 production by mediating C/EBP␣ serine 21 phosphorylation by PKC␦. Significance: Our data suggest that IL-32␤ functions as an intracellular regulator of IL-10 production.

Edited by Beat ImhofKeywords: IL-32b IL-32d IL-10 PKCd U937 Isoform interaction a b s t r a c t There is growing evidence for multifunctional properties of IL-32. We previously demonstrated that IL-32b upregulates IL-10 production through the association with PKCd. In this study, we examined the effects of other IL-32 isoforms on IL-10 production. We found that IL-32d decreased IL-10 production and investigated the inhibitory mechanism of IL-32d. We showed that IL-32d suppressed IL-32b binding to PKCd by interacting with IL-32b. The inhibitory effect of IL-32d on IL-32b association with PKCd was further verified by immuno-fluorescence staining. The co-localization of IL-32b and PKCd around the nuclear membrane was disrupted by IL-32d. Our data therefore indicate that IL-32d plays an inhibitory role against IL-32b function, which also suggests that IL-32 may be regulated by its own isoform. Structured summary of protein interactions:PKC delta physically interacts with IL-32 beta by anti bait coimmunoprecipitation (View interaction) IL-32 beta physically interacts with PKC delta by anti tag coimmunoprecipitation (View interaction) IL-32 beta physically interacts with IL-32 delta by anti tag coimmunoprecipitation (1, 2) PKC delta and IL-32 beta colocalize by fluorescence microscopy (view interaction)