Gene interactions and pathways from curated databases and text-mining
Bone 2001, PMID: 11248656

Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation in human osteoblasts: evidence for involvement of receptor subunits IL-13R, IL-13Ralpha, and IL-4Ralpha.

Frost, A; Jonsson, K B; Brändström, H; Ljunghall, S; Nilsson, O; Ljunggren, O

Interleukin-13 (IL-13) inhibits cell proliferation and stimulates interleukin-6 (IL-6) formation in isolated human osteoblasts (hOBs). Because the related cytokine, interleukin-4 (IL-4), is known to exert effects similar to IL-13 in other tissues, and because IL-4 has been implicated as a regulator of bone metabolism, we compared the effects of IL-13 and IL-4 on cell proliferation, IL-6 synthesis, the expression of osteoblastic phenotypic markers in hOB cultures. Also, the receptor proteins mediating these effects in hOBs have been partly characterized. IL-4 and IL-13 dose-dependently inhibited [(3)H]-thymidine incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6 into culture supernatants. IL-13 and IL-4 also increased the mRNA levels of IL-6, as measured by RNAse protection assay. Furthermore, IL-13 and IL-4 dose-dependently enhanced alkaline phosphatase (ALP) activity, but did not affect osteocalcin or collagen type I synthesis. IL-4 was tenfold more potent than IL-13 in inducing both ALP activity and IL-6 secretion, whereas the cytokines were equipotent as inhibitors of cell proliferation. The expression of mRNA for receptor subunits previously implicated in IL-4 and IL-13 signaling was investigated by reverse transcriptase-polymerase chain reaction. IL-13R, IL-13Ralpha, and IL-4Ralpha mRNA were repeatedly detected in hOBs, whereas mRNA for IL-2Rgamma(C) was not detected. Receptor-blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13, indicating that both cytokines utilize this receptor subunit in signaling. However, the antibodies did not affect the IL-4/-13-induced inhibition of [(3)H]-thymidine incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs. We conclude that the cytokines IL-13 and IL-4, through sharing of receptor components, induce similar effects on hOBs, causing inhibition of cell proliferation, stimulation of IL-6, and enhanced ALP activity.

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Text Mining Data

IL-6 → Interleukin (IL)-13: " Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation in human osteoblasts : evidence for involvement of receptor subunits IL-13R, IL-13Ralpha, and IL-4Ralpha "

IL-6 → IL-4: " Interleukin (IL)-13 and IL-4 inhibit proliferation and stimulate IL-6 formation in human osteoblasts : evidence for involvement of receptor subunits IL-13R, IL-13Ralpha, and IL-4Ralpha "

IL-6 → IL-13: " IL-4 and IL-13 dose-dependently inhibited [ ( 3 ) H ] -thymidine incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6 into culture supernatants "

IL-6 → IL-4: " IL-4 and IL-13 dose-dependently inhibited [ ( 3 ) H ] -thymidine incorporation into the DNA of human osteoblasts and stimulated secretion of IL-6 into culture supernatants "

IL-6 → IL-13: " IL-13 and IL-4 also increased the mRNA levels of IL-6 , as measured by RNAse protection assay "

IL-6 → IL-4: " IL-13 and IL-4 also increased the mRNA levels of IL-6 , as measured by RNAse protection assay "

alkaline phosphatase (ALP) → IL-13: " Furthermore, IL-13 and IL-4 dose-dependently enhanced alkaline phosphatase (ALP) activity, but did not affect osteocalcin or collagen type I synthesis "

alkaline phosphatase (ALP) → IL-4: " Furthermore, IL-13 and IL-4 dose-dependently enhanced alkaline phosphatase (ALP) activity, but did not affect osteocalcin or collagen type I synthesis "

IL-6 → IL-13: " Receptor blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13 , indicating that both cytokines utilize this receptor subunit in signaling "

IL-6 → IL-4: " Receptor blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13, indicating that both cytokines utilize this receptor subunit in signaling "

alkaline phosphatase (ALP) → IL-4/-13: " However, the antibodies did not affect the IL-4/-13 induced inhibition of [ ( 3 ) H ] -thymidine incorporation or the stimulation of alkaline phosphatase (ALP) , suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs "

alkaline phosphatase (ALP) → IL-4/-13: " However, the antibodies did not affect the IL-4/-13 induced inhibition of [ ( 3 ) H ] -thymidine incorporation or the stimulation of alkaline phosphatase (ALP) , suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs "

IL-4Ralpha → IL-4/-13: " However, the antibodies did not affect the IL-4/-13 induced inhibition of [ ( 3 ) H ] -thymidine incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs "

IL-4Ralpha → IL-4/-13: " However, the antibodies did not affect the IL-4/-13 induced inhibition of [ ( 3 ) H ] -thymidine incorporation or the stimulation of alkaline phosphatase (ALP), suggesting that IL-4Ralpha does not mediate these effects of IL-4/-13 in hOBs "

Manually curated Databases

No curated data.