Abstract
Interaction between thyroid hormones and the immune system is reported in the literature. Thyroid hormones, thyroxine, T4, but also T3, act non-genomically through mechanisms that involve a plasma membrane receptor αvβ3 integrin, a co-receptor for insulin-like growth factor-1 (IGF-1). Previous data from our laboratory show a crosstalk between thyroid hormones and IGF-1 because thyroid hormones inhibit the IGF-1-stimulated glucose uptake and cell proliferation in L-6 myoblasts, and the effects are mediated by integrin αvβ3. IGF-1 also behaves as a chemokine, being an important factor for tissue regeneration after damage. In the present study, using THP-1 human leukemic monocytes, expressing αvβ3 integrin in their cell membrane, we focused on the crosstalk between thyroid hormones and either IGF-1 or monocyte chemoattractant protein-1 (MCP-1), studying cell migration and proliferation stimulated by the two chemokines, and the role of αvβ3 integrin, using inhibitors of αvβ3 integrin and downstream pathways. Our results show that IGF-1 is a potent chemoattractant in THP-1 monocytes, stimulating cell migration, and thyroid hormone inhibits the effect through αvβ3 integrin. Thyroid hormone also inhibits IGF-1-stimulated cell proliferation through αvβ3 integrin, an example of a crosstalk between genomic and non-genomic effects. We also studied the effects of thyroid hormone on cell migration and proliferation induced by MCP-1, together with the pathways involved, by a pharmacological approach and docking simulation. Our findings show a different downstream signaling for IGF-1 and MCP-1 in THP-1 monocytes mediated by the plasma membrane receptor of thyroid hormones, integrin αvβ3.
Highlights
Thyroid hormones 3,5,3 -triiodo-L-thyronine (T3) and Lthyroxine (T4) give rise to a wide range of effects on metabolism, growth, and development (Yen, 2001)
Non-genomic mechanisms of thyroid hormone action rely upon transduction of the hormone signal by kinases such as mitogen-activated protein kinase (MAPK) (Lin et al, 1999a; D’Arezzo et al, 2004; Lei et al, 2004, 2008; Cao et al, 2005; Davis et al, 2005; Cohen et al, 2011) or phosphoinositide 3kinase (PI3K) (Bergh et al, 2005; Hiroi et al, 2006; Incerpi et al, 2014; Davis et al, 2016) that are cytoplasmic in location, but once they are activated may move to other intracellular compartments
We evaluated the effect of T4 on THP-1 cell migration in the presence of both monocyte chemoattractant protein-1 (MCP-1) and insulin-like growth factor-1 (IGF-1)
Summary
Thyroid hormones 3,5,3 -triiodo-L-thyronine (T3) and Lthyroxine (T4) give rise to a wide range of effects on metabolism, growth, and development (Yen, 2001). Non-genomic mechanisms of thyroid hormone action rely upon transduction of the hormone signal by kinases such as mitogen-activated protein kinase (MAPK) (Lin et al, 1999a; D’Arezzo et al, 2004; Lei et al, 2004, 2008; Cao et al, 2005; Davis et al, 2005; Cohen et al, 2011) or phosphoinositide 3kinase (PI3K) (Bergh et al, 2005; Hiroi et al, 2006; Incerpi et al, 2014; Davis et al, 2016) that are cytoplasmic in location, but once they are activated may move to other intracellular compartments. Thyroid hormones are able to modulate the activity of growth factors such as EGF and transforming growth factor-α (TGF-α) (Lin et al, 1999b; Shih et al, 2004)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
