Insulin-Like Growth Factor-1 Receptor Regulation in Activated Human T Lymphocytes

Abstract

Objective: To investigate the kinetics of insulin-like growth factor-1 receptor (IGF-1R) expression in PHA-stimulated T lymphocytes. Methods: IGF-1R protein and mRNA were detected by flow cytometry and RT-PCR respectively, between 0 and 48 h after cell activation. Results: Few minutes after T lymphocytes were activated, internalization of the IGF-1R from the cell membrane was observed, achieving the lower level between 1 and 6 h and was accompanied by a reduction in its mRNA. This was followed by re-expression of IGF-1R on the cell surface and an increase in IGF-1R mRNA levels in the cytoplasm, reaching levels higher than those recorded initially after 48 h activation. Conclusion: This down- and up-regulation suggests that restoration of IGF-1R would be the result of receptor recycling and de novo synthesis and highlights its importance for T lymphocyte proliferation.

Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases?

“…This reduction may be transient and associated with depressed steady-state IGF-IR mRNA levels (Segretin et al, 2003). A similar finding could be demonstrated in Jurkat cells, and addition of IGF-I to the culture me-208 SMITH dium enhanced this effect (Schillaci et al, 1998).…”

“…ϩ CD45RO ϩ cells activated by phytohemagglutinin or after exposure to recall antigens in vitro display considerably lower levels of IGF-IR than do inactive lymphocytes (Kooijman et al, 1995a,b,c;Schillaci et al, 1998;Segretin et al, 2003). This reduction may be transient and associated with depressed steady-state IGF-IR mRNA levels (Segretin et al, 2003).…”

MicroRNA let-7i induced autophagy to protect T cell from apoptosis by targeting IGF1R

“…For instance, overrepresentation of T cells expressing IGF1R has been found in Graves' disease [24], but IGF1R levels trend downward in several aging and chronic diseases [25]. Activation of adult lymphocytes causes a decline in IGF1R expression [16,18,26] whereas activation of cord blood mononuclear cells (CBMC) leads to an increase in IGF1R expression, which was thought to be dependent on the activated status [27]. Based on these discrepant data, we investigated the expression of IGF1R in T cells from AS patients.…”

“…IGF1R is located on T cell surface determining activation of T cells [16]. The increasing evidences have demonstrated down-regulation of IGF1R at the early stage of T cells activation followed by increasing IGF1R level along with T cells activation [17,18].…”

Dendritic Cell Differentiation and Immune Tolerance to Insulin-Related Peptides in Igf2-Deficient Mice

“…IGF-2 could also influence the apoptotic phenomenon to promote T cell survival in the same way as IGF-1, which influences T cell survival via Akt and JNK pathway (36). The role played by IGF-2 could be mediated through IGF-1R, which binds both IGF-1 and IGF-2, and is regulated during T-lymphocyte activation (37). These different ways are under current investigation.…”