Based on these data, we propose that early genes may play multifunctional roles in tumor growth control, but specificity for the growth arrest action of IL-1 is determined by the composite early gene induction program.
IL-2-expanded 444P.3 cells, tested on day 104 in culture, expressed mRNA for tumor necrosis factor (TNF), IL-2 and tumor growth factor beta (TGF-beta) but not for IL-1, lymphotoxin or granulocyte/macrophage-colony stimulating factor (GM-CSF).
In addition, using chimeric constructs of the stromelysin promoter linked to the bacterial gene chloramphenicol acetyltransferase (CAT), we show that the elements required for the tumor promoter phorbol myristate acetate (PMA), epidermal growth factor (EGF), and interleukin 1 beta (IL-1 beta) induction are contained on a 307 base pair fragment which includes approximately 270 base pairs (bp) of 5'-flanking DNA.
The acute monocytic leukemia cell line THP-1 secretes predominantly IL-1 beta after treatment with bacterial lipopolysaccharide and tumour promoting phorbol ester (PMA).
In this case, very high serum levels of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) were found before tumor excision, associated with inflammatory signs including major hyper-gamma-globulinemia.
Interleukin-1 (IL-1) has a number of fundamental immunoregulatory, hematologic, metabolic, and physiologic effects and thus is instrumental in the coordination of tissue interactions, such as wound healing, inflammation, and host tumor response.
Mezerein-differentiated THP-1 cells secrete interleukin-1 beta as well as a tumor cell growth inhibitory factor whose basal level is increased in response to interferon-gamma.
Addition of the tumor promoter, okadaic acid (OA), or cytokine, interleukin 1 (IL-1), but not serum or platelet-derived growth factor (PDGF), induced increased expression of the est transcript.
IL-6 mRNA was expressed in tumor tissue in 83% of the cases but only in one case in normal mucosa (p < 0.001); serum levels of IL-6 did not show any correlation with IL-6 mRNA; IL-1 beta transcripts were present in all tumor tissue samples; no IL-4 expression was detected; IL-2 mRNA was only present in two tumors; IL-2R(p55) mRNA was found in 58% of tumors but not in normal mucosae (p = 0.005).
In vitro experiments on a panel of human bladder tumour cell lines (EJ18, MGH-U1, RT4, RT112) indicate that our genetically modified mycobacteria are more effective than wild-type at inducing or up-regulating the expression of intracellular adhesion molecule-1 and the secretion of an array of proinflammatory cytokines [interleukin-1 (IL-1), IL-6, IL-8, granulocyte-macrophage colony-stimulating factor].
The observed altered gene expression may be related to biological phenotypes of hepatic tumors, and IL-1ra in particular may positively influence tumor cell growth through its antagonism of IL-1.
The mRNA expression of inflammatory cytokines including interleukin-1 (IL-1), IL-6, and IL-8 in the tumor tissue was also demonstrated by a reverse transcriptase-polymerase chain reaction analysis.
Decreased irradiation induction of TGF-beta1, TGF-beta2, TGF-beta3, MIF, TNF-alpha, and IL-1 at 24 h was detected in lungs, but not orthotopic tumors from MnSOD-PL-injected mice (P < 0.001).
The data suggest that local IL-1beta secretion during the vaccination phase can provoke or augment protective immune responses to B16 melanoma cells, which are otherwise not recorded in mice bearing B16 tumors.
These results indicate that IL-1 may be used as an autocrine growth factor by a number of tumors in which activation of Raf plays an important role in transformation and suggest that blockade of IL-1 signaling may be an approach to limiting the growth of certain tumors.
We found a significant association between the IL-1 polymorphisms and increased risk for tumor development in patients with intestinal-type gastric carcinoma.
A comparative study with other soluble inflammatory mediators showed that intratumoral levels of MIF were significantly associated with those of interleukin-1 beta, suggesting that interactions between tumor cells and tumor-associated macrophages play an important role in the up-regulation of MIF.
Proinflammatory cytokine IL-1 beta promotes tumor growth of Lewis lung carcinoma by induction of angiogenic factors: in vivo analysis of tumor-stromal interaction.
Here we review the effects of microenvironmental and tumor cell-associated IL-1 on malignant processes, in experimental tumor models and in cancer patients.